TMPRSS2-mediated SARS-CoV-2 uptake boosts innate immune activation, enhances cytopathology, and drives convergent virus evolution.

The accessory protease transmembrane protease serine 2 (TMPRSS2) enhances severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uptake into ACE2-expressing cells, although how increased entry impacts downstream viral and host processes remains unclear. To investigate this in more detail, we performed infection assays in engineered cells promoting ACE2-mediated entry with and without TMPRSS2 coexpression. Electron microscopy and inhibitor experiments indicated TMPRSS2-mediated cell entry was associated with increased virion internalization into endosomes, and partially dependent upon clathrin-mediated endocytosis. TMPRSS2 increased panvariant uptake efficiency and enhanced early rates of virus replication, transcription, and secretion, with variant-specific profiles observed. On the host side, transcriptional profiling confirmed the magnitude of infection-induced antiviral and proinflammatory responses were linked to uptake efficiency, with TMPRSS2-assisted entry boosting early antiviral responses. In addition, TMPRSS2-enhanced infections increased rates of cytopathology, apoptosis, and necrosis and modulated virus secretion kinetics in a variant-specific manner. On the virus side, convergent signatures of cell-uptake-dependent innate immune induction were recorded in viral genomes, manifesting as switches in dominant coupled Nsp3 residues whose frequencies were correlated to the magnitude of the cellular response to infection. Experimentally, we demonstrated that selected Nsp3 mutations conferred enhanced interferon antagonism. More broadly, we show that TMPRSS2 orthologues from evolutionarily diverse mammals facilitate panvariant enhancement of cell uptake. In summary, our study uncovers previously unreported associations, linking cell entry efficiency to innate immune activation kinetics, cell death rates, virus secretion dynamics, and convergent selection of viral mutations. These data expand our understanding of TMPRSS2's role in the SARS-CoV-2 life cycle and confirm its broader significance in zoonotic reservoirs and animal models.

Marine degradation and ecotoxicity of conventional, recycled and compostable plastic bags.

Plastic bags are currently a major component of marine litter, causing aesthetical nuisance, and undesirable effects on marine fauna that ingest them or are entangled. Plastic litter also rises concern on the ecotoxicological effects due to the potential toxicity of the chemical additives leached in aquatic environments. Conventional plastic bags are made of polyethylene, either from first use or recycled, but regulations restricting single-use plastics and limiting lightweight carrier bags (<50 µm thickness) have fostered the replacement of thin PE bags by compostable materials advertised as safer for the environment. In this study, we assess the degradation of commercially available plastic bags in marine conditions at two scales: aquariums (60 days) and outdoors flow-through mesocosm (120 days). Strength at break point and other tensile strength parameters were used as ecologically relevant endpoints to track mechanical degradation. Ecotoxicity has been assessed along the incubation period using the sensitive Paracentrotus lividus embryo test. Whereas PE bags did not substantially lose their mechanical properties within the 60 d aquarium exposures, compostable bags showed remarkable weight loss and tensile strength decay, some of them fragmenting in the aquarium after 3-4 weeks. Sediment pore water inoculum promoted a more rapid degradation of compostable bags, while nutrient addition pattern did not affect the degradation rate. Longer-term mesocosms exposures supported these findings, as well as pointed out the influence of the microbial processes on the degradation efficiency of compostable/bioplastic bags. Compostable materials, in contrast toPE, showed moderate toxicity on sea-urchin larvae, partially associated to degradation of these materials, but the environmental implications of these findings remain to be assessed. These methods proved to be useful to classify plastic materials, according to their degradability in marine conditions, in a remarkably shorter time than current standard tests and promote new materials safer for the marine fauna.

Myelin dystrophy in the aging prefrontal cortex leads to impaired signal transmission and working memory decline: a multiscale computational study.

Normal aging leads to myelin alternations in the rhesus monkey dorsolateral prefrontal cortex (dlPFC), which are often correlated with cognitive impairment. It is hypothesized that remyelination with shorter and thinner myelin sheaths partially compensates for myelin degradation, but computational modeling has not yet explored these two phenomena together systematically. Here, we used a two-pronged modeling approach to determine how age-related myelin changes affect a core cognitive function: spatial working memory. First we built a multicompartment pyramidal neuron model fit to monkey dlPFC data, with axon including myelinated segments having paranodes, juxtaparanodes, internodes, and tight junctions, to quantify conduction velocity (CV) changes and action potential (AP) failures after demyelination and subsequent remyelination in a population of neurons. Lasso regression identified distinctive parameter sets likely to modulate an axon's susceptibility to CV changes following demyelination versus remyelination. Next we incorporated the single neuron results into a spiking neural network model of working memory. While complete remyelination nearly recovered axonal transmission and network function to unperturbed levels, our models predict that biologically plausible levels of myelin dystrophy, if uncompensated by other factors, can account for substantial working memory impairment with aging. The present computational study unites empirical data from electron microscopy up to behavior on aging, and has broader implications for many demyelinating conditions, such as multiple sclerosis or schizophrenia.

UV Dosage Unveils Toxic Properties of Weathered Commercial Bioplastic Bags.

Previous studies indicated that weathered conventional plastics and bioplastics pose ecotoxicological risks. Here, the effects of artificial and natural weathering on the ecotoxicity of three compostable bags and a conventional polyethylene (PE) bag are investigated. With that aim, a 21-day artificial indoor weathering experiment featuring UV light, UV-filtered light, and darkness was run simultaneously to a 120-day outdoor littoral mesocosm exposure featuring natural light, UV-filtered light, and shaded conditions. Acute toxicity of so-weathered plastic specimens was tested in vivo using the sensitive Paracentrotus lividus sea-urchin embryo test. PE was nontoxic from the beginning and did not gain toxicity due to UV weathering. In contrast, for bioplastics, dry artificial UV weathering increased toxicity in comparison to the dark control. Weathering in outdoor mesocosm led to a rapid loss of toxic properties due to leaching in rainwater. With a higher UV dosage, a plastic-type-dependent regain of toxicity was observed, most likely driven by enhanced availability or transformation of functional additives or due to bioplastic degradation products. PE showed moderate UV absorbance, while bioplastics showed high UV absorbance. This study highlights the potential of biodegradable plastics to pose enhanced ecotoxicological risk due to weathering under environmentally relevant conditions.

Neuronal properties of pyramidal cells in lateral prefrontal cortex of the aging rhesus monkey brain are associated with performance deficits on spatial working memory but not executive function.

Age-related declines in cognitive abilities occur as early as middle-age in humans and rhesus monkeys. Specifically, performance by aged individuals on tasks of executive function (EF) and working memory (WM) is characterized by greater frequency of errors, shorter memory spans, increased frequency of perseverative responses, impaired use of feedback and reduced speed of processing. However, how aging precisely differentially impacts specific aspects of these cognitive functions and the distinct brain areas mediating cognition are not well understood. The prefrontal cortex (PFC) is known to mediate EF and WM and is an area that shows a vulnerability to age-related alterations in neuronal morphology. In the current study, we show that performance on EF and WM tasks exhibited significant changes with age, and these impairments correlate with changes in biophysical properties of layer 3 (L3) pyramidal neurons in lateral LPFC (LPFC). Specifically, there was a significant age-related increase in excitability of L3 LPFC pyramidal neurons, consistent with previous studies. Further, this age-related hyperexcitability of LPFC neurons was significantly correlated with age-related decline on a task of WM, but not an EF task. The current study characterizes age-related performance on tasks of WM and EF and provides insight into the neural substrates that may underlie changes in both WM and EF with age.

A Practical Tool for the Assessment of Polymer Biodegradability in Marine Environments Guides the Development of Truly Biodegradable Plastics.

Environmental persistence is one of the few shortcomings of plastic materials. As a consequence, alternative plastics labeled as compostable are replacing polyolefins in some commercial applications, such as food bags and trash bags. A rapid, high-throughput, and environmentally relevant method to assess the potential biodegradability in marine conditions is used to assess these materials already on the market, as well as novel bio-based polymers still in development. By fitting experimental data to a non-linear logistic model, ultimate biodegradability can be calculated without regard for incubation time. Whereas the commercial products show negligible or very low marine biodegradability, one of the novel materials exceeds the 20% biodegradation threshold relative to fully marine biodegradable PHB after 28 days. In addition, the sensitivity of the method can be enhanced and its duration reduced, at the expense of labor-demanding preconditioning of the microbial inoculum, by increasing the bacterial density in the incubation vessels. In contrast, pre-exposure of the inoculum to plastic, either in laboratory or field conditions, does not enhance the performance of the test.

Effect of culture conditions at lab-scale on metabolite composition and antibacterial and antibiofilm activities of Dunaliella tertiolecta.

Dunaliella tertiolecta RCC6 was cultivated indoors in glass bubble column photobioreactors operated under batch and semi-continuous regimens and using two different conditions of light and temperature. Biomass was harvested by centrifugation, frozen, and then lyophilized. The soluble material was obtained by sequential extraction of the lyophilized biomass with solvents with a gradient of polarity (hexane, ethyl acetate, and methanol) and its metabolic composition was investigated through nuclear magnetic resonance (NMR) spectroscopy. The effect of light on chlorophyll biosynthesis was clearly shown through the relative intensities of the 1 H NMR signals due to pheophytins. The highest signal intensity was observed for the biomasses obtained at lower light intensity, resulting in a lower light availability per cell. Under high temperature and light conditions, the 1 H NMR spectra of the hexane extracts showed an incipient accumulation of triacylglycerols. In these conditions and under semi-continuous regimen, an enhancement of ß-carotene and sterols production was observed. The antibacterial and antibiofilm activities of the extracts were also tested. Antibacterial activity was not detected, regardless of culture conditions. In contrast, the minimal biofilm inhibitory concentrations (MBICs) against Escherichia coli for the hexane extract obtained under semi-continuous regimen using high temperature and irradiance conditions was promising.

Mesocosm trials reveal the potential toxic risk of degrading bioplastics to marine life.

If biodegradable plastics tackle the marine plastic pollution problem sufficiently remains questionable. To gain more insight in degradability, performance, and the impact of degradation on the toxicity, commercial bags made from two biodegradable plastics and one conventional plastic (PE) were exposed for 120 days in a mesocosm featuring benthic, pelagic, and littoral habitat simulations. Degradability was assessed as weight loss, and specimens were tested for toxicity using Paracentrotus lividus sea-urchin larvae after different exposure times. Both biodegradable bags showed degradation within 120 days, with the littoral simulation showing the highest and the pelagic simulation the lowest decay. Disregarding habitat, the home-compostable plastic showed higher marine degradation than the industrial-compostable material. The relevant initial toxicity of both biopolymers was lost within 7 days of exposure, pointing towards easily leachable chemical additives as its cause. Interestingly, littoral exposed specimens gained toxicity after 120 days, suggesting UV- induced modifications that increase biopolymer toxicity.

Is a compostable plastic biodegradable in the sea? A rapid standard protocol to test mineralization in marine conditions.

Due to environmental persistence, lack of a proper land-based waste management, and global circulation, marine ecosystems are especially threatened by plastics. The search for alternatives to conventional oil-based polymers gave rise to novel materials commercialized under different "green" labels based on compostability. However, current international standards are not effective in predicting actual biodegradability of plastic objects in natural scenarios, and degradation of these novel bioplastics in marine conditions is unwarranted. We present a simple and rapid standard protocol based on their biological oxygen demand, intended to support policy-makers and plastic industry in the search for truly marine-biodegradable plastics. Improvements include: development of an environmentally relevant nutrient formulation following Redfield ratio (106C:16 N:1P); use of a natural inoculum representative of marine habitats (sediment pore water); standardization of the test material by grinding to particles below 250 µm to shorten the incubation period, and selection of a truly biodegradable biopolymer (PHB), used as positive control. This protocol was successfully applied to show that commercial compostable plastics are not biodegradable in marine environments.

Layer-specific pyramidal neuron properties underlie diverse anterior cingulate cortical motor and limbic networks.

The laminar cellular and circuit mechanisms by which the anterior cingulate cortex (ACC) exerts flexible control of motor and affective information for goal-directed behavior have not been elucidated. Using multimodal tract-tracing, in vitro patch-clamp recording and computational approaches in rhesus monkeys (M. mulatta), we provide evidence that specialized motor and affective network dynamics can be conferred by layer-specific biophysical and structural properties of ACC pyramidal neurons targeting two key downstream structures -the dorsal premotor cortex (PMd) and the amygdala (AMY). AMY-targeting neurons exhibited significant laminar differences, with L5 more excitable (higher input resistance and action potential firing rates) than L3 neurons. Between-pathway differences were found within L5, with AMY-targeting neurons exhibiting greater excitability, apical dendritic complexity, spine densities, and diversity of inhibitory inputs than PMd-targeting neurons. Simulations using a pyramidal-interneuron network model predict that these layer- and pathway-specific single-cell differences contribute to distinct network oscillatory dynamics. L5 AMY-targeting networks are more tuned to slow oscillations well-suited for affective and contextual processing timescales, while PMd-targeting networks showed strong beta/gamma synchrony implicated in rapid sensorimotor processing. These findings are fundamental to our broad understanding of how layer-specific cellular and circuit properties can drive diverse laminar activity found in flexible behavior.

Microalgae and Cyanobacteria Strains as Producers of Lipids with Antibacterial and Antibiofilm Activity.

Lipids are one of the primary metabolites of microalgae and cyanobacteria, which enrich their utility in the pharmaceutical, feed, cosmetic, and chemistry sectors. This work describes the isolation, structural elucidation, and the antibiotic and antibiofilm activities of diverse lipids produced by different microalgae and cyanobacteria strains from two European collections (ACOI and LEGE-CC). Three microalgae strains and one cyanobacteria strain were selected for their antibacterial and/or antibiofilm activity after the screening of about 600 strains carried out under the NoMorFilm European project. The total organic extracts were firstly fractionated using solid phase extraction methods, and the minimum inhibitory concentration and minimal biofilm inhibitory concentration against an array of human pathogens were determined. The isolation was carried out by bioassay-guided HPLC-DAD purification, and the structure of the isolated molecules responsible for the observed activities was determined by HPLC-HRESIMS and NMR methods. Sulfoquinovosyldiacylglycerol, monogalactosylmonoacylglycerol, sulfoquinovosylmonoacylglycerol, α-linolenic acid, hexadeca-4,7,10,13-tetraenoic acid (HDTA), palmitoleic acid, and lysophosphatidylcholine were found among the different active sub-fractions selected. In conclusion, cyanobacteria and microalgae produce a great variety of lipids with antibiotic and antibiofilm activity against the most important pathogens causing severe infections in humans. The use of these lipids in clinical treatments alone or in combination with antibiotics may provide an alternative to the current treatments.

Assessment of Toxicity and Biodegradability of Poly(vinyl alcohol)-Based Materials in Marine Water.

Due to the continuous rise in conventional plastic production and the deficient management of plastic waste, industry is developing alternative plastic products made of biodegradable or biobased polymers. The challenge nowadays is to create a new product that combines the advantages of conventional plastics with environmentally friendly properties. This study focuses on the assessment of the potential impact that polyvinyl alcohol (PVA)-based polymers may have once they are released into the marine environment, in terms of biodegradation in seawater (assessed by the percentage of the Theoretical Oxygen Demand, or % ThOD, of each compound) and aquatic toxicity, according to the standard toxicity test using Paracentrotus lividus larvae. We have tested three different materials: two glycerol-containing PVA based ones, and another made from pure PVA. Biodegradation of PVA under marine conditions without an acclimated inoculum seems to be negligible, and it slightly improves when the polymer is combined with glycerol, with a 5.3 and 8.4% ThOD achieved after a period of 28 days. Toxicity of pure PVA was also negligible (<1 toxic units, TU), but slightly increases when the material included glycerol (2.2 and 2.3 TU). These results may contribute to a better assessment of the behavior of PVA-based polymers in marine environments. Given the low biodegradation rates obtained for the tested compounds, PVA polymers still require further study in order to develop materials that are truly degradable in real marine scenarios.

Terpenoids and Polyphenols as Natural Antioxidant Agents in Food Preservation.

Synthetic antioxidant food additives, such as BHA, BHT and TBHQ, are going through a difficult time, since these products generate a negative perception in consumers. This has generated an increased pressure on food manufacturers to search for safer natural alternatives like phytochemicals (such as polyphenols, including flavonoids, and essential oils rich in terpenoids, including carotenoids). These plant bioactive compounds have antioxidant activities widely proven in in vitro tests and in diverse food matrices (meat, fish, oil and vegetables). As tons of food are wasted every year due to aesthetic reasons (lipid oxidation) and premature damage caused by inappropriate packaging, there is an urgent need for natural antioxidants capable of replacing the synthetic ones to meet consumer demands. This review summarizes industrially interesting antioxidant bioactivities associated with terpenoids and polyphenols with respect to the prevention of lipid oxidation in high fat containing foods, such as meat (rich in saturated fat), fish (rich in polyunsaturated fat), oil and vegetable products, while avoiding the generation of rancid flavors and negative visual deterioration (such as color changes due to oxidized lipids). Terpenoids (like monoterpenes and carotenoids) and polyphenols (like quercetin and other flavonoids) are important phytochemicals with a broad range of antioxidant effects. These phytochemicals are widely distributed in fruits and vegetables, including agricultural waste, and are remarkably useful in food preservation, as they show bioactivity as plant antioxidants, able to scavenge reactive oxygen and nitrogen species, such as superoxide, hydroxyl or peroxyl radicals in meat and other products, contributing to the prevention of lipid oxidation processes in food matrices.

Elderly patients, isometric exercise, and native vascular access maturation: An unsolved question?

INTRODUCTION: The number of elderly patients undergoing hemodialysis is steadily increasing. The choice and management of vascular access (VA) in these patients are difficult, and the role of postoperative isometric exercises on native VA maturation in the elderly population is not clearly established. OBJECTIVES: To assess the effect of postoperative isometric exercises on native VA maturation in patients older than 75 years with advanced chronic kidney disease. METHODOLOGY: This was a randomized single-center study over a 24-month period. Postoperative isometric exercises were performed in the exercise group (EG), while the control group (CG) received usual care. Demographic data, muscle strength (using handgrip [HG] dynamometer), Doppler ultrasound (DUS), incidence of VA complications, and clinical and DUS maturation were assessed at 4 and 8 weeks. RESULTS: A total of 27 patients were included (EG: 14, CG: 13). The mean age of the patients was 79.9 ± 2.8 years; 74.1% were men, and 59.2% had radiocephalic VA. Demographic data, HG, and DUS measurements were similar at baseline. DUS measurements significantly increased in both groups at the end of the study. A significant increase in HG (19.1 ± 7.8 kg vs. 22.9 ± 9.7 kg, P = 0.001) and the highest clinical (CG vs. EG: 46.2% vs. 78.6%; P = 0.049) and DUS maturation (CG vs. EG: 30.8% vs. 71.4%; P = 0.041) were observed in the EG at 8 weeks. Globally, medical or surgical VA complications were lower in the EG and mainly included significant stenosis (CG vs. EG: 23.1% vs. 7.1%), although no significant differences were observed. CONCLUSIONS: Once a native VA is indicated in elderly patients, postoperative isometric exercise should be considered in order to improve the odds of achieving a mature functional arteriovenous fistula. Further studies are required to support our findings in this population.

Plant Phytochemicals in Food Preservation: Antifungal Bioactivity: A Review.

Synthetic food additives generate a negative perception in consumers. This fact generates an important pressure on food manufacturers, searching for safer natural alternatives. Phytochemicals (such as polyphenols and thiols) and plant essential oils (terpenoids) possess antimicrobial activities that are able to prevent food spoilage due to fungi (e.g., Aspergillus, Penicillium) and intoxications (due to mycotoxins), both of which are important economic and health problems worldwide. This review summarizes industrially interesting antifungal bioactivities from the three main types of plant nutraceuticals: terpenoids (as thymol), polyphenols (as resveratrol) and thiols (as allicin) as well as some of the mechanisms of action. These phytochemicals are widely distributed in fruits and vegetables and are very useful in food preservation as they inhibit growth of important spoilage and pathogenic fungi, affecting especially mycelial growth and germination. Terpenoids and essential oils are the most abundant group of secondary metabolites found in plant extracts, especially in common aromatic plants, but polyphenols are a more remarkable group of bioactive compounds as they show a broad array of bioactivities.

Polyethylene microplastics do not increase bioaccumulation or toxicity of nonylphenol and 4-MBC to marine zooplankton.

Global production of synthetic polymers, led by polyethylene (PE), rose steadily in the last decades, and marine ecosystems are considered as a global sink. Although PE is not biodegradable, in coastal areas it fragments into microplastics (MP) readily taken up by biota, and have been postulated as vectors of hydrophobic chemicals to marine organisms. We have tested this hypothesis using two organisms representative of the marine plankton, the holoplanktonic copepod Acartia clausi, and the meroplanktonic larva of the Paracentrotus lividus sea-urchin, and two model chemicals with similar hydrophobic properties, the 4-n-Nonylphenol and the 4-Methylbenzylidene-camphor used as plastic additive and UV filter in cosmetics. Both test species actively ingested the MP particles. However, the presence of MP never increased the bioaccumulation of neither model chemicals, nor their toxicity to the exposed organisms. Bioaccumulation was a linear function of waterborne chemical disregarding the level of MP. Toxicity, assessed by the threshold (EC10) and median (EC50) effect levels, was either independent of the level of MP or even in some instances significantly decreased in the presence of MPs. These consistent results challenge the assumption that MP act as vectors of hydrophobic chemicals to planktonic marine organisms.

Network Models Predict That Pyramidal Neuron Hyperexcitability and Synapse Loss in the dlPFC Lead to Age-Related Spatial Working Memory Impairment in Rhesus Monkeys.

Behavioral studies have shown spatial working memory impairment with aging in several animal species, including humans. Persistent activity of layer 3 pyramidal dorsolateral prefrontal cortex (dlPFC) neurons during delay periods of working memory tasks is important for encoding memory of the stimulus. In vitro studies have shown that these neurons undergo significant age-related structural and functional changes, but the extent to which these changes affect neural mechanisms underlying spatial working memory is not understood fully. Here, we confirm previous studies showing impairment on the Delayed Recognition Span Task in the spatial condition (DRSTsp), and increased in vitro action potential firing rates (hyperexcitability), across the adult life span of the rhesus monkey. We use a bump attractor model to predict how empirically observed changes in the aging dlPFC affect performance on the Delayed Response Task (DRT), and introduce a model of memory retention in the DRSTsp. Persistent activity-and, in turn, cognitive performance-in both models was affected much more by hyperexcitability of pyramidal neurons than by a loss of synapses. Our DRT simulations predict that additional changes to the network, such as increased firing of inhibitory interneurons, are needed to account for lower firing rates during the DRT with aging reported in vivo. Synaptic facilitation was an essential feature of the DRSTsp model, but it did not compensate fully for the effects of the other age-related changes on DRT performance. Modeling pyramidal neuron hyperexcitability and synapse loss simultaneously led to a partial recovery of function in both tasks, with the simulated level of DRSTsp impairment similar to that observed in aging monkeys. This modeling work integrates empirical data across multiple scales, from synapse counts to cognitive testing, to further our understanding of aging in non-human primates.

A 2-Tier standard method to test the toxicity of microplastics in marine water using Paracentrotus lividus and Acartia clausi larvae.

A 2-tier standardized protocol was designed to test the toxicity of microplastics to planktonic organisms. This approach uses sea urchin (Paracentrotus lividus) and copepod (Acartia clausi) larvae because they are common biological models in marine research, and standard methods for toxicity testing with regulatory applications are available. In Tier I, leachates obtained at a 100 to 1 liquid to solid ratio are tested, and toxic units are calculated using a probit dose-response model to quantify the toxicity of the plastics. In Tier II, which is conducted only if significant toxicity (> 1 toxic unit) is found in Tier I, particles less than 20 µm in size are tested at concentrations between 0.1 and 10 mg L-1 , and a toxicity threshold suitable for ranking materials according to their toxicity is obtained from the 10% effect concentration (EC10) values. Results point to chemical additives as being responsible for the toxicity found in certain plastic materials. This process is suitable for both a priori identification of the hazard posed by plastic objects in the aquatic environment, and a posteriori assessment of environmental risk caused by microplastic pollution. The method also provides a quantitative procedure appropriate for ranking plastic materials according to their toxicity to aquatic organisms. Environ Toxicol Chem 2019;38:630-637. © 2018 SETAC.

Survival After Endovascular Abdominal Aortic Aneurysm Repair in a Population with a Low Incidence of Coronary Artery Disease.

BACKGROUND: Endovascular aortic aneurysm repair (EVAR) is a prophylactic procedure, so the decision to operate should consider, as recent guidelines suggest, the life expectancy of the patient. Several models for predicting life span have been already designed, but little is known about how intervened patients evolve in Southern European Countries, where the incidence of coronary artery disease, the main cause of death among these subjects, is low. METHODS: We conducted a retrospective analysis of 176 consecutive patients who underwent elective EVAR at the Vascular Surgery Department of the Hospital del Mar (Barcelona, Spain) during 2000-2014. Cox regressions were performed to identify preoperative factors associated with long-term survival after EVAR, and a risk model was developed. RESULTS: Three- and five-year survival rates were 73.9 and 53.9 %, respectively. During the follow-up, 72 deaths (40.9 %) were registered, cancer being the most frequent cause (41.7 %). Preoperative variables negatively associated with long-term survival were serum creatinine ≥ 150 µmol/L (HR 2.5; 95 % CI 1.4-4.2), chronic obstructive pulmonary disease (HR 1.9; 95 % CI 1.2-3.1), atrial fibrillation (HR 2.0; 95 % CI 1.2-3.4), and prior cancer history (HR 1.9; 95 % CI 1.2-3.1). Distal pulses present in both lower limbs were marginally associated with survival (HR 0.65; 95 % CI 0.4-1.07). The survival predictive model showed a good discrimination capacity (C statistic = 0.703; 95 % CI 0.641-0.765). CONCLUSIONS: Long-term survival of patients submitted to EVAR in our setting was worse than expected and markedly related to cancer. Our study suggests that predictive models for long-term survival after EVAR may be influenced by regional characteristics of the intervened population. This effect should be taken in consideration in the decision-making process of these patients.

Ameloblastic fibro-odontoma associated with a retained molar in an Oldenburg mare.

An 11-year-old Oldenburg mare presented with a 3-month history of weight loss and swelling of the posterior right mandible. Physical examination and radiographs showed a soft-tissue mass in the right mandible with foci of mineralization, periosteal proliferation, and a retained molar. The tumor increased in size over several weeks, and the mare was euthanized. On necropsy, a 24 cm × 15 cm × 15 cm firm, white mass had obliterated the posterior right mandible. The mass was multinodular with discrete clusters of blood-filled cystic spaces. Histologically, the mass was composed of neoplastic odontogenic epithelium and pulpal mesenchyme with an accumulation of eosinophilic material resembling dentin or enamel. Microscopic and immunohistochemical staining features of the neoplasm were most consistent with an ameloblastic fibro-odontoma.