Effects of balloon injury on neointimal hyperplasia in steptozotocin-induced diabetes and in hyperinsulinemic nondiabetic pancreatic islet-transplanted rats.

BACKGROUND: The mechanisms of increased neointimal hyperplasia after coronary interventions in diabetic patients are still unknown. METHODS AND RESULTS: Glucose and insulin effects on in vitro vascular smooth muscle cell (VSMC) proliferation and migration were assessed. The effect of balloon injury on neointimal hyperplasia was studied in streptozotocin-induced diabetic rats with or without adjunct insulin therapy. To study the effect of balloon injury in nondiabetic rats with hyperinsulinemia, pancreatic islets were transplanted under the kidney capsule in normal rats. Glucose did not increase VSMC proliferation and migration in vitro. In contrast, insulin induced a significant increase in VSMC proliferation and migration in cell cultures. Furthermore, in VSMC culture, insulin increased MAPK activation. A reduction in neointimal hyperplasia was consistently documented after vascular injury in hyperglycemic streptozotocin-induced diabetic rats. Insulin therapy significantly increased neointimal hyperplasia in these rats. This effect of hyperinsulinemia was totally abolished by transfection on the arterial wall of the N17H-ras-negative mutant gene. Finally, after experimental balloon angioplasty in hyperinsulinemic nondiabetic islet-transplanted rats, a significant increase in neointimal hyperplasia was observed. CONCLUSIONS: In rats with streptozotocin-induced diabetes, balloon injury was not associated with an increase in neointimal formation. Exogenous insulin administration in diabetic rats and islet transplantation in nondiabetic rats increased both blood insulin levels and neointimal hyperplasia after balloon injury. Hyperinsulinemia through activation of the ras/MAPK pathway, rather than hyperglycemia per se, seems to be of crucial importance in determining the exaggerated neointimal hyperplasia after balloon angioplasty in diabetic animals

Yield, quality, antioxidant, and sensorial properties of diced tomato as affected by genotype and industrial processing in Southern Italy

Research was carried out on processing tomato in Southern Italy in order to compare four round-prismatic type hybrids oriented to diced produce (4420, Miceno, Nemabrix, Impact as a control). The hybrid Nemabrix attained the highest marketable yield (180.9 t ha–1, due to both the highest number of fruit per plant and their mean weight (103.7 and 70 g, respectively), and it was not significantly different from the other genotypes in terms of processing efficiency both as a total and along dicing chain (67.8% and 65.6%, respectively). Lycopene attained the highest concentration in Nemabrix (155 mg kg–1), and β–carotene was most concentrated in 4420 and Miceno (2.8 mg kg–1). Significant differences arose between the genotypes with regard to the sensorial variables aspect, colour, taste, firmness, and fresh taste

Drug management of atrial fibrillation in light of guidelines and current evidence: an Italian Survey on behalf of Italian Association of Arrhythmology and Cardiac Pacing

AimAtrial fibrillation is a multifaceted disease requiring personalized treatment, in accordance with current ESC guidelines. Despite a wide range of literature, we still have various aspects dividing the opinion of the experts in rate control, rhythm control and thromboembolic prophylaxis. The aim of this survey was to provide a country-wide picture of current practice regarding atrial fibrillation pharmacological management according to a patient's characteristics.MethodsData were collected using an in-person survey that was administered to members of the Italian Association of Arrhythmology and Cardiac Pacing.ResultsWe collected data from 106 physicians, working in 72 Italian hospitals from 15 of 21 regions. Our work evidenced a high inhomogeneity in atrial fibrillation management regarding rhythm control, rate control and thromboembolic prophylaxis in both acute and chronic patients. This element was more pronounced in settings in which literature shows a lack of evidence and, consequently, the indications provided by the guidelines are weak or absent.ConclusionThis National survey evidenced a high inhomogeneity in current approaches adopted for atrial fibrillation management by a sample of Italian cardiologist experts in arrhythmia management. Further studies are needed to explore if these divergences are associated with different long-term outcomes

Performance of a multi-sensor implantable defibrillator algorithm for heart failure monitoring in the presence of atrial fibrillation

AIMS: The HeartLogic Index combines data from multiple implantable cardioverter defibrillators (ICDs) sensors and has been shown to accurately stratify patients at risk of heart failure (HF) events. We evaluated and compared the performance of this algorithm during sinus rhythm and during long-lasting atrial fibrillation (AF). METHODS AND RESULTS: HeartLogic was activated in 568 ICD patients from 26 centres. We found periods of ≥30 consecutive days with an atrial high-rate episode (AHRE) burden <1 h/day and periods with an AHRE burden ≥20 h/day. We then identified patients who met both criteria during the follow-up (AHRE group, n = 53), to allow pairwise comparison of periods. For control purposes, we identified patients with an AHRE burden <1 h throughout their follow-up and implemented 2:1 propensity score matching vs. the AHRE group (matched non-AHRE group, n = 106). In the AHRE group, the rate of alerts was 1.2 [95% confidence interval (CI): 1.0-1.5]/patient-year during periods with an AHRE burden <1 h/day and 2.0 (95% CI: 1.5-2.6)/patient-year during periods with an AHRE-burden ≥20 h/day (P = 0.004). The rate of HF hospitalizations was 0.34 (95% CI: 0.15-0.69)/patient-year during IN-alert periods and 0.06 (95% CI: 0.02-0.14)/patient-year during OUT-of-alert periods (P < 0.001). The IN/OUT-of-alert state incidence rate ratio of HF hospitalizations was 8.59 (95% CI: 1.67-55.31) during periods with an AHRE burden <1 h/day and 2.70 (95% CI: 1.01-28.33) during periods with an AHRE burden ≥20 h/day. In the matched non-AHRE group, the rate of HF hospitalizations was 0.29 (95% CI: 0.12-0.60)/patient-year during IN-alert periods and 0.04 (95% CI: 0.02-0.08)/patient-year during OUT-of-alert periods (P < 0.001). The incidence rate ratio was 7.11 (95% CI: 2.19-22.44). CONCLUSION: Patients received more alerts during periods of AF. The ability of the algorithm to identify increased risk of HF events was confirmed during AF, despite a lower IN/OUT-of-alert incidence rate ratio in comparison with non-AF periods and non-AF patients. CLINICAL TRIAL REGISTRATION: http://clinicaltrials.gov/Identifier: NCT02275637

β1-Adrenergic Receptor and Sphingosine- 1-Phosphate Receptor 1 Reciprocal Down-Regulation Influences Cardiac Hypertrophic Response and Progression Toward Heart Failure: Protective Role of S1PR1 Cardiac Gene Therapy

YesThe Sphingosine-1-phosphate receptor 1 (S1PR1) and β1-adrenergic receptor (β1AR) are G protein-coupled receptors (GPCRs) expressed in the heart. These two GPCRs have opposing actions on adenylyl cyclase due to differential G protein-coupling. Importantly, both of these receptors can be regulated by the actions of GPCR kinase-2 (GRK2), which triggers desensitization and down-regulation processes. Although, classical signaling paradigms suggest that simultaneous activation of β1ARs and S1PR1s in a myocyte would simply be opposing action on cAMP production, in this report we have uncovered a direct interaction between these two receptors with a regulatory involvement of GRK2. In HEK293 cells overexpressing both β1AR and S1PR1, we demonstrate that β1AR down-regulation can occur after sphingosine 1-phosphate (S1PR1 agonist) stimulation while S1PR1 down-regulation can be triggered by isoproterenol (βAR agonist) treatment. This cross-talk between these two distinct GPCRs appears to have physiological significance since they interact and show reciprocal regulation in mouse hearts undergoing chronic βAR stimulation and also in a rat model of post-ischemic heart failure (HF). We demonstrate that restoring cardiac plasma membrane levels of S1PR1 produce beneficial effects counterbalancing deleterious β1AR overstimulation in HF

Yield, quality and antioxidants of peeled tomato as affected by genotype and industrial processing in southern Italy

Research was carried out on processing tomato in San Severo (Tavoliere delle Puglie, Foggia, Italy) in order to compare four long-type fruit hybrids oriented to peeled produce (Abbundo, Umex, Superpeel, Taylor), using a randomized complete block design with three replicates. The hybrid Superpeel reached the highest marketable yield due to the highest fruit number and mean weight; along the peeling chain, Umex and Taylor showed the highest processing efficiency. Titratable acidity and sodium were highest in Taylor fruits, whereas the highest fiber content was detected in Abbundo fruits. Compared to pre-processing fruits, peeled tomatoes showed increased values of total and soluble solids as well as reducing sugars, but decreased sugar ratio and colour. The highest concentrations of antioxidants in processed fruits were recorded in Umex for lycopene and in Superpeel for β-carotene. Compared to pre-processing fruits, in peeled tomatoes lycopene and β-carotene concentrations remained stable and polyphenols increased referring to fresh weight. The hybrids examined did not show univocal trends in terms of sensorial features

Signaling from β1- and β2-adrenergic receptors is defined by differential interactions with PDE4

β1- and β2-adrenergic receptors (βARs) are highly homologous, yet they play clearly distinct roles in cardiac physiology and pathology. Myocyte contraction, for instance, is readily stimulated by β1AR but not β2AR signaling, and chronic stimulation of the two receptors has opposing effects on myocyte apoptosis and cell survival. Differences in the assembly of macromolecular signaling complexes may explain the distinct biological outcomes. Here, we demonstrate that β1AR forms a signaling complex with a cAMP-specific phosphodiesterase (PDE) in a manner inherently different from a β2AR/β-arrestin/PDE complex reported previously. The β1AR binds a PDE variant, PDE4D8, in a direct manner, and occupancy of the receptor by an agonist causes dissociation of this complex. Conversely, agonist binding to the β2AR is a prerequisite for the recruitment of a complex consisting of β-arrestin and the PDE4D variant, PDE4D5, to the receptor. We propose that the distinct modes of interaction with PDEs result in divergent cAMP signals in the vicinity of the two receptors, thus, providing an additional layer of complexity to enforce the specificity of β1- and β2-adrenoceptor signaling

A standard protocol for reporting species distribution models

Species distribution models (SDMs) constitute the most common class of models across ecology, evolution and conservation. The advent of ready-to-use software packages and increasing availability of digital geoinformation have considerably assisted the application of SDMs in the past decade, greatly enabling their broader use for informing conservation and management, and for quantifying impacts from global change. However, models must be fit for purpose, with all important aspects of their development and applications properly considered. Despite the widespread use of SDMs, standardisation and documentation of modelling protocols remain limited, which makes it hard to assess whether development steps are appropriate for end use. To address these issues, we propose a standard protocol for reporting SDMs, with an emphasis on describing how a study's objective is achieved through a series of modeling decisions. We call this the ODMAP (Overview, Data, Model, Assessment and Prediction) protocol, as its components reflect the main steps involved in building SDMs and other empirically-based biodiversity models. The ODMAP protocol serves two main purposes. First, it provides a checklist for authors, detailing key steps for model building and analyses, and thus represents a quick guide and generic workflow for modern SDMs. Second, it introduces a structured format for documenting and communicating the models, ensuring transparency and reproducibility, facilitating peer review and expert evaluation of model quality, as well as meta-analyses. We detail all elements of ODMAP, and explain how it can be used for different model objectives and applications, and how it complements efforts to store associated metadata and define modelling standards. We illustrate its utility by revisiting nine previously published case studies, and provide an interactive web-based application to facilitate its use. We plan to advance ODMAP by encouraging its further refinement and adoption by the scientific community

A global reptile assessment highlights shared conservation needs of tetrapods

Comprehensive assessments of species’ extinction risks have documented the extinction crisis and underpinned strategies for reducing those risks. Global assessments reveal that, among tetrapods, 40.7% of amphibians, 25.4% of mammals and 13.6% of birds are threatened with extinction. Because global assessments have been lacking, reptiles have been omitted from conservation-prioritization analyses that encompass other tetrapods. Reptiles are unusually diverse in arid regions, suggesting that they may have different conservation needs. Here we provide a comprehensive extinction-risk assessment of reptiles and show that at least 1,829 out of 10,196 species (21.1%) are threatened—confirming a previous extrapolation and representing 15.6 billion years of phylogenetic diversity. Reptiles are threatened by the same major factors that threaten other tetrapods—agriculture, logging, urban development and invasive species—although the threat posed by climate change remains uncertain. Reptiles inhabiting forests, where these threats are strongest, are more threatened than those in arid habitats, contrary to our prediction. Birds, mammals and amphibians are unexpectedly good surrogates for the conservation of reptiles, although threatened reptiles with the smallest ranges tend to be isolated from other threatened tetrapods. Although some reptiles—including most species of crocodiles and turtles—require urgent, targeted action to prevent extinctions, efforts to protect other tetrapods, such as habitat preservation and control of trade and invasive species, will probably also benefit many reptiles.Neil Cox, Bruce E. Young, Philip Bowles, Miguel Fernandez, Julie Marin, Giovanni Rapacciuolo, Monika Böhm, Thomas M. Brooks, S. Blair Hedges, Craig Hilton-Taylor, Michael Hoffmann, Richard K. B. Jenkins, Marcelo F. Tognelli, Graham J. Alexander, Allen Allison, Natalia B. Ananjeva, Mark Auliya, Luciano Javier Avila, David G. Chapple, Diego F. Cisneros-Heredia, Harold G. Cogger, Guarino R. Colli, Anslem de Silva, Carla C. Eisemberg, Johannes Els, Ansel Fong G., Tandora D. Grant, Rodney A. Hitchmough, Djoko T. Iskandar, Noriko Kidera, Marcio Martins, Shai Meiri, Nicola J. Mitchell, Sanjay Molur, Cristiano de C. Nogueira, Juan Carlos Ortiz, Johannes Penner, Anders G. J. Rhodin, Gilson A. Rivas, Mark-Oliver Rödel, Uri Roll, Kate L. Sanders, Georgina Santos-Barrera, Glenn M. Shea, Stephen Spawls, Bryan L. Stuart, Krystal A. Tolley, Jean-François Trape, Marcela A. Vidal, Philipp Wagner, Bryan P. Wallace, Yan Xi