Sheep head frame validation for CT and MRI studies

Abstract IntroductionsAim of EDEN 2020 project’s Milestone 5 is the development of a steerable catheter for CED system in glioblastoma therapy. The VET group is involved in realization and validation of the proper animal model.Materials and methodsIn this part of the study two fresh sheep’s head from the local slaughter were used.The heads were located into an ad hoc Frame system based on anatomical measures and CT images, producted by Renishaw plc partner in this project. The frame was adapted and every components were checked for the ex vivo validation tests.CT imaging was taken in Lodi at Università degli studi di Milano, Facoltà di Medicina Veterinaria, with CT scanner and MRI imaging was taken in La Cittadina, CremonaResultsSystem validation was approved by the ex vivo trial.The frame system doesn’t compromise the imaging acquisition in MRI and CT systems.Every system components are functional to their aims.DiscussionThe Frame system is adapted to the sheep head. It is composed by elements able to lock the head during the imaging acquisition. Frame system is characterized by a support base helpings the animals to keep the head straight forward during imaging time, under general anesthesia. The design of these device support the airways anatomy, avoiding damaging or obstruction of airflows during anesthesia period.The role of elements like mouth bar and ovine head pins is to lock the head in a stable position during imaging acquisition; fixing is guaranteed by V shape head pins, that are arranged against the zygomatic arches. Lateral compression forces to the cranium, and the V shape pins avoid the vertical shifting of the head and any kind of rotations. (fig. 1

Sheep brain atlas creation. Diffusion tensor imaging and Scanning electron microscope in sheep brain analysis

IntroductionsAim of EDEN 2020 project is the development of a steerable catheter for CED system in glioblastoma therapy. The VET group is involved in realization and validation of the proper animal model.For surgical planning purpose a Diffusion Tensor Imaging (DTI) of white matter tracts in the sheep is necessary to identify the target points useful for the catheter introduction.The analysis of the sheep brain under a Scanning Electron Microscope (SEM) is required to understand any alterations due to the catheter introduction and to fluids injection during CED administration. Materials and methodsAnimals were treated in accordance with the European Communities Council directive (86/609/EEC), to the laws and regulations on animal welfare enclosed in D.L.G.S. 26/2014A total of five 70 kg female, one year old, sheep were used for the study.All animals, under general anesthesia, underwent to Magnetic Resonance Imaging (MRI) acquisition. MRI scanner used was Philips Ingenia 1.5 Tesla system.Once the DTI imaging were acquired the animals were euthanased, sheep brain was collected and samples of white matter tracts obtained with disposable biopsy punches of 1.5-2 mm of diameter.The samples were fixed, stained in Osmium tetroxide (OsO4) and then embedded with two different protocols (cold curing vs thermal curing) in resin for the Focused Ion Beam (FIB) SEM analyses. Results and discussionAll the DTI images were uploaded to TrackVis software and major white matter fiber tracts analysed. Corticospinal tract, visual radiation, fornix and fronto-occipital fasciculus were identified.Corticospinal tract was identified as major white matter tract in sheep brain and useful as target area for the research aims.For the SEM analysis the thermal protocol was recognised as better curing methods for the research purpose than cold curing one. ConclusionThe data acquired in this study are still submitted to analysis. AcknowledgmentThe project has received funding from the European Union’s EU Research and Innovation programme Horizon 2020 (no 688279)

REFLEXÕES ACERCA DE INICIATIVAS AGROECOLÓGICAS NO LITORAL NORTE DO RS

As iniciativas agroecológicas representam uma proposta alternativa para um modelo de desenvolvimento rural sustentável. O objetivo deste estudo foi conhecer e analisar as iniciativas agroecológicas no município de Caraá, Litoral Norte do estado do Rio Grande do Sul. Para atender ao objetivo, foram realizadas quatro entrevistas a representantes de instituições municipais e nove entrevistas à representantes de iniciativas agroecológicas. Os resultados do estudo, permitem inferir que, as iniciativas possuem menos de cinco anos de experiência, com importante participação feminina no trabalho e na gestão, presença de público neo-rural e ampla diversidade de atividades remuneradas, mostrando a pluriatividade destes estabelecimentos. Conclui-se, portanto que estas iniciativas são importantes e exercem influência na economia local, na qualidade de vida e na permanência da população no meio rural

JNK1 ablation in mice confers long-term metabolic protection from diet-induced obesity at the cost of moderate skin oxidative damage

Obesity and insulin resistance are associated with oxidative stress, which may be implicated in the progression of obesity-related diseases. The kinase JNK1 has emerged as a promising drug target for the treatment of obesity and type 2 diabetes. JNK1 is also a key mediator of the oxidative stress response, which can promote cell death or survival, depending on the magnitude and context of its activation. In this article, we describe a study in which the long-term effects of JNK1 inactivation on glucose homeostasis and oxidative stress in obese mice were investigated for the first time. Mice lacking JNK1 (JNK1−/−) were fed an obesogenic high-fat diet (HFD) for a long period. JNK1−/− mice fed an HFD for the long term had reduced expression of antioxidant genes in their skin, more skin oxidative damage, and increased epidermal thickness and inflammation compared with the effects in control wild-type mice. However, we also observed that the protection from obesity, adipose tissue inflammation, steatosis, and insulin resistance, conferred by JNK1 ablation, was sustained over a long period and was paralleled by decreased oxidative damage in fat and liver. We conclude that compounds targeting JNK1 activity in brain and adipose tissue, which do not accumulate in the skin, may be safer and most effective.— Becattini, B., Zani, F., Breasson, L., Sardi, C., D’Agostino, V. G., Choo, M.-K., Provenzani, A., Park, J. M., Solinas, G. JNK1 ablation in mice confers long-term metabolic protection from diet-induced obesity at the cost of moderate skin oxidative damage

Loss of the Actin Remodeler Eps8 Causes Intestinal Defects and Improved Metabolic Status in Mice

In a variety of organisms, including mammals, caloric restriction improves metabolic status and lowers the incidence of chronic-degenerative diseases, ultimately leading to increased lifespan. Here we show that knockout mice for Eps8, a regulator of actin dynamics, display reduced body weight, partial resistance to age- or diet-induced obesity, and overall improved metabolic status. Alteration in the liver gene expression profile, in behavior and metabolism point to a calorie restriction-like phenotype in Eps8 knockout mice. Additionally, and consistent with a calorie restricted metabolism, Eps8 knockout mice show increased lifespan. The metabolic alterations in Eps8 knockout mice correlated with a significant reduction in intestinal fat absorption presumably caused by a 25% reduction in intestinal microvilli length. Our findings implicate actin dynamics as a novel variable in the determination of longevity. Additionally, our observations suggest that subtle differences in energy balance can, over time, significantly affect bodyweight and metabolic status in mice

A role for adipose tissue de novo lipogenesis in glucose homeostasis during catch-up growth : a randle cycle favoring fat storage

Catch-up growth, a risk factor for type 2 diabetes, is characterized by hyperinsulinemia and accelerated body fat recovery. Using a rat model of semistarvation-refeeding that exhibits catch-up fat, we previously reported that during refeeding on a low-fat diet, glucose tolerance is normal but insulin-dependent glucose utilization is decreased in skeletal muscle and increased in adipose tissue, where de novo lipogenic capacity is concomitantly enhanced. Here we report that isocaloric refeeding on a high-fat (HF) diet blunts the enhanced in vivo insulin-dependent glucose utilization for de novo lipogenesis (DNL) in adipose tissue. These are shown to be early events of catch-up growth that are independent of hyperphagia and precede the development of overt adipocyte hypertrophy, adipose tissue inflammation, or defective insulin signaling. These results suggest a role for enhanced DNL as a glucose sink in regulating glycemia during catch-up growth, which is blunted by exposure to an HF diet, thereby contributing, together with skeletal muscle insulin resistance, to the development of glucose intolerance. Our findings are presented as an extension of the Randle cycle hypothesis, whereby the suppression of DNL constitutes a mechanism by which dietary lipids antagonize glucose utilization for storage as triglycerides in adipose tissue, thereby impairing glucose homeostasis during catch-up growth

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe