Under- and over-water halves of Gyrinidae beetle eyes harbor different corneal nanocoatings providing adaptation to the water and air environments.

Whirligig beetles (Gyrinidae) inhabit water surfaces and possess unique eyes which are split into the overwater and underwater parts. In this study we analyze the micro- and nanostructure of the split eyes of two Gyrinidae beetles genera, Gyrinus and Orectochilus. We find that corneae of the overwater ommatidia are covered with maze-like nanostructures, while the corneal surface of the underwater eyes is smooth. We further show that the overwater nanostructures possess no anti-wetting, but the anti-reflective properties with the spectral preference in the range of 450-600 nm. These findings illustrate the adaptation of the corneal nanocoating of the two halves of an insect's eye to two different environments. The novel natural anti-reflective nanocoating we describe may find future technological applications.

Bone regeneration and stem cells.

?  Introduction ?  Bone fracture healing and healing problems ?  Biomaterial scaffolds and tissue engineering in bone formation -  Bone tissue engineering -  Biomaterial scaffolds -  Synthetic scaffolds -  Micro- and nanostructural properties of scaffolds -  Conclusion ?  Mesenchymal stem cells and osteogenesis -  Bone tissue -  Origin of osteoblasts -  Isolation and characterization of bone marrow derived MSC -  In vitro differentiation of MSC into osteoblast lineage cells -  In vivo differentiation of MSC into bone -  Factors and pathways controlling osteoblast differentiation of hMSC -  Defining the relationship between osteoblast and adipocyte differentiation from MSC -  MSC and sex hormones -  Effect of aging on osteoblastogenesis -  Conclusion ?  Embryonic, foetal and adult stem cells in osteogenesis -  Cell-based therapies for bone -  Specific features of bone cells needed to be advantageous for clinical use -  Development of therapeutic biological agents -  Clinical application concerns -  Conclusion ?  Platelet-rich plasma (PRP), growth factors and osteogenesis -  PRP effects in vitro on the cells involved in bone repair -  PRP effects on osteoblasts -  PRP effects on osteoclasts -  PRP effects on endothelial cells -  PRP effects in vivo on experimental animals -  The clinical use of PRP for bone repair -  Non-union -  Distraction osteogenesis -  Spinal fusion -  Foot and ankle surgery -  Total knee arthroplasty -  Odontostomatology and maxillofacial surgery -  Conclusion ?  Molecular control of osteogenesis -  TGF-β signalling -  FGF signalling -  IGF signalling -  PDGF signalling -  MAPK signalling pathway -  Wnt signalling pathway -  Hedgehog signalling -  Notch signalling -  Ephrin signalling -  Transcription factors regulating osteoblast differentiation -  Conclusion ?  Summary This invited review covers research areas of central importance for orthopaedic and maxillofacial bone tissue repair, including normal fracture healing and healing problems, biomaterial scaffolds for tissue engineering, mesenchymal and foetal stem cells, effects of sex steroids on mesenchymal stem cells, use of platelet-rich plasma for tissue repair, osteogenesis and its molecular markers. A variety of cells in addition to stem cells, as well as advances in materials science to meet specific requirements for bone and soft tissue regeneration by addition of bioactive molecules, are discussed.

Iridophores and not carotenoids account for chromatic variation of carotenoid-basedcColoration in Common lizards (Lacerta vivipara).

Abstract Carotenoids typically need reflective background components to shine. Such components, iridophores, leucophores, and keratin- and collagen-derived structures, are generally assumed to show no or little environmental variability. Here, we investigate the origin of environmentally induced variation in the carotenoid-based ventral coloration of male common lizards (Lacerta vivipara) by investigating the effects of dietary carotenoids and corticosterone on both carotenoid- and background-related reflectance. We observed a general negative chromatic change that was prevented by β-carotene supplementation. However, chromatic changes did not result from changes in carotenoid-related reflectance or skin carotenoid content but from changes in background-related reflectance that may have been mediated by vitamin A. An in vitro experiment showed that the encountered chromatic changes most likely resulted from changes in iridophore reflectance. Our findings demonstrate that chromatic variation in carotenoid-based ornaments may not exclusively reflect differences in integumentary carotenoid content and, hence, in qualities linked to carotenoid deposition (e.g., foraging ability, immune response, or antioxidant capacity). Moreover, skin carotenoid content and carotenoid-related reflectance were related to male color polymorphism, suggesting that carotenoid-based coloration of male common lizards is a multicomponent signal, with iridophores reflecting environmental conditions and carotenoids reflecting genetically based color morphs.

Characterization of gravitational rock slope deformations at different spatial scales based on field, remote sensing and numerical approaches

Rock slope instabilities such as rock slides, rock avalanche or deep-seated gravitational slope deformations are widespread in Alpine valleys. These phenomena represent at the same time a main factor that control the mountain belts erosion and also a significant natural hazard that creates important losses to the mountain communities. However, the potential geometrical and dynamic connections linking outcrop and slope-scale instabilities are often unknown. A more detailed definition of the potential links will be essential to improve the comprehension of the destabilization processes and to dispose of a more complete hazard characterization of the rock instabilities at different spatial scales. In order to propose an integrated approach in the study of the rock slope instabilities, three main themes were analysed in this PhD thesis: (1) the inventory and the spatial distribution of rock slope deformations at regional scale and their influence on the landscape evolution, (2) the influence of brittle and ductile tectonic structures on rock slope instabilities development and (3) the characterization of hazard posed by potential rock slope instabilities through the development of conceptual instability models. To prose and integrated approach for the analyses of these topics, several techniques were adopted. In particular, high resolution digital elevation models revealed to be fundamental tools that were employed during the different stages of the rock slope instability assessment. A special attention was spent in the application of digital elevation model for detailed geometrical modelling of past and potential instabilities and for the rock slope monitoring at different spatial scales. Detailed field analyses and numerical models were performed to complete and verify the remote sensing approach. In the first part of this thesis, large slope instabilities in Rhone valley (Switzerland) were mapped in order to dispose of a first overview of tectonic and climatic factors influencing their distribution and their characteristics. Our analyses demonstrate the key influence of neotectonic activity and the glacial conditioning on the spatial distribution of the rock slope deformations. Besides, the volumes of rock instabilities identified along the main Rhone valley, were then used to propose the first estimate of the postglacial denudation and filling of the Rhone valley associated to large gravitational movements. In the second part of the thesis, detailed structural analyses of the Frank slide and the Sierre rock avalanche were performed to characterize the influence of brittle and ductile tectonic structures on the geometry and on the failure mechanism of large instabilities. Our observations indicated that the geometric characteristics and the variation of the rock mass quality associated to ductile tectonic structures, that are often ignored landslide study, represent important factors that can drastically influence the extension and the failure mechanism of rock slope instabilities. In the last part of the thesis, the failure mechanisms and the hazard associated to five potential instabilities were analysed in detail. These case studies clearly highlighted the importance to incorporate different analyses and monitoring techniques to dispose of reliable and hazard scenarios. This information associated to the development of a conceptual instability model represents the primary data for an integrated risk management of rock slope instabilities. - Les mouvements de versant tels que les chutes de blocs, les éboulements ou encore les phénomènes plus lents comme les déformations gravitaires profondes de versant représentent des manifestations courantes en régions montagneuses. Les mouvements de versant sont à la fois un des facteurs principaux contrôlant la destruction progressive des chaines orogéniques mais aussi un danger naturel concret qui peut provoquer des dommages importants. Pourtant, les phénomènes gravitaires sont rarement analysés dans leur globalité et les rapports géométriques et mécaniques qui lient les instabilités à l'échelle du versant aux instabilités locales restent encore mal définis. Une meilleure caractérisation de ces liens pourrait pourtant représenter un apport substantiel dans la compréhension des processus de déstabilisation des versants et améliorer la caractérisation des dangers gravitaires à toutes les échelles spatiales. Dans le but de proposer un approche plus globale à la problématique des mouvements gravitaires, ce travail de thèse propose trois axes de recherche principaux: (1) l'inventaire et l'analyse de la distribution spatiale des grandes instabilités rocheuses à l'échelle régionale, (2) l'analyse des structures tectoniques cassantes et ductiles en relation avec les mécanismes de rupture des grandes instabilités rocheuses et (3) la caractérisation des aléas rocheux par une approche multidisciplinaire visant à développer un modèle conceptuel de l'instabilité et une meilleure appréciation du danger . Pour analyser les différentes problématiques traitées dans cette thèse, différentes techniques ont été utilisées. En particulier, le modèle numérique de terrain s'est révélé être un outil indispensable pour la majorité des analyses effectuées, en partant de l'identification de l'instabilité jusqu'au suivi des mouvements. Les analyses de terrain et des modélisations numériques ont ensuite permis de compléter les informations issues du modèle numérique de terrain. Dans la première partie de cette thèse, les mouvements gravitaires rocheux dans la vallée du Rhône (Suisse) ont été cartographiés pour étudier leur répartition en fonction des variables géologiques et morphologiques régionales. En particulier, les analyses ont mis en évidence l'influence de l'activité néotectonique et des phases glaciaires sur la distribution des zones à forte densité d'instabilités rocheuses. Les volumes des instabilités rocheuses identifiées le long de la vallée principale ont été ensuite utilisés pour estimer le taux de dénudations postglaciaire et le remplissage de la vallée du Rhône lié aux grands mouvements gravitaires. Dans la deuxième partie, l'étude de l'agencement structural des avalanches rocheuses de Sierre (Suisse) et de Frank (Canada) a permis de mieux caractériser l'influence passive des structures tectoniques sur la géométrie des instabilités. En particulier, les structures issues d'une tectonique ductile, souvent ignorées dans l'étude des instabilités gravitaires, ont été identifiées comme des structures très importantes qui contrôlent les mécanismes de rupture des instabilités à différentes échelles. Dans la dernière partie de la thèse, cinq instabilités rocheuses différentes ont été étudiées par une approche multidisciplinaire visant à mieux caractériser l'aléa et à développer un modèle conceptuel trois dimensionnel de ces instabilités. A l'aide de ces analyses on a pu mettre en évidence la nécessité d'incorporer différentes techniques d'analyses et de surveillance pour une gestion plus objective du risque associée aux grandes instabilités rocheuses.

Disentangling in vivo the effects of iron content and atrophy on the ageing human brain.

Evidence from magnetic resonance imaging (MRI) studies shows that healthy aging is associated with profound changes in cortical and subcortical brain structures. The reliable delineation of cortex and basal ganglia using automated computational anatomy methods based on T1-weighted images remains challenging, which results in controversies in the literature. In this study we use quantitative MRI (qMRI) to gain an insight into the microstructural mechanisms underlying tissue ageing and look for potential interactions between ageing and brain tissue properties to assess their impact on automated tissue classification. To this end we acquired maps of longitudinal relaxation rate R1, effective transverse relaxation rate R2* and magnetization transfer - MT, from healthy subjects (n=96, aged 21-88 years) using a well-established multi-parameter mapping qMRI protocol. Within the framework of voxel-based quantification we find higher grey matter volume in basal ganglia, cerebellar dentate and prefrontal cortex when tissue classification is based on MT maps compared with T1 maps. These discrepancies between grey matter volume estimates can be attributed to R2* - a surrogate marker of iron concentration, and further modulation by an interaction between R2* and age, both in cortical and subcortical areas. We interpret our findings as direct evidence for the impact of ageing-related brain tissue property changes on automated tissue classification of brain structures using SPM12. Computational anatomy studies of ageing and neurodegeneration should acknowledge these effects, particularly when inferring about underlying pathophysiology from regional cortex and basal ganglia volume changes.

Differential phosphorylation of tau proteins during kitten brain development and Alzheimer's disease.

Differential distribution and phosphorylation of tau proteins were studied in developing kitten brain by using several antibodies, and was compared to phosphorylation in Alzheimer's disease. Several antibodies demonstrated the presence of phosphorylated tau proteins during kitten brain development and identified pathological structures in human brain tissue. Antibody AD2, recognized tau in kittens and adult cats, but reacted in Alzheimer's tissue only with a pathological tau form. Antibody AT8 was prominent in developing kitten neurons and was found in axons and dendrites. After the first postnatal month this phosphorylation type disappeared from axons. Furthermore, dephosphorylation of kitten tau with alkaline phosphatase abolished immunoreactivity of AT8, but not that of AD2, pointing to a protection of the AD2 epitope in cats. Tau proteins during early cat brain development are phosphorylated at several sites that are also phosphorylated in paired helical filaments during Alzheimer's disease. In either event, phosphorylation of tau may play a crucial role to modulate microtubule dynamics, contributing to increased microtubule instability and promoting growth of processes during neuronal development or changing dynamic properties of the cytoskeleton and contributing to the formation of pathological structures in neurodegenerative diseases.

Objective assessment of image quality in conventional and digital mammography taking into account dynamic range.

The goal of this work is to develop a method to objectively compare the performance of a digital and a screen-film mammography system in terms of image quality. The method takes into account the dynamic range of the image detector, the detection of high and low contrast structures, the visualisation of the images and the observer response. A test object, designed to represent a compressed breast, was constructed from various tissue equivalent materials ranging from purely adipose to purely glandular composition. Different areas within the test object permitted the evaluation of low and high contrast detection, spatial resolution and image noise. All the images (digital and conventional) were captured using a CCD camera to include the visualisation process in the image quality assessment. A mathematical model observer (non-prewhitening matched filter), that calculates the detectability of high and low contrast structures using spatial resolution, noise and contrast, was used to compare the two technologies. Our results show that for a given patient dose, the detection of high and low contrast structures is significantly better for the digital system than for the conventional screen-film system studied. The method of using a test object with a large tissue composition range combined with a camera to compare conventional and digital imaging modalities can be applied to other radiological imaging techniques. In particular it could be used to optimise the process of radiographic reading of soft copy images.

Organismos filantrópicos y no gubernamentales en el desarrollo de nuevas ciencias y tecnologías: el caso de las micro y nanotecnologías en México

RESUMEN: La emergencia de nuevas ciencias y tecnologías vienen acompañadas de nuevas dinámicas en la producción, el uso y la diseminación de nuevos conocimientos científicos y tecnológicos. Estas nuevas dinámicas se reflejan en la reorganización de las actividades científicas, en la creación o la reorientación de nuevas temáticas en la investigación, en la emergencia de nuevas preocupaciones y debates sobre los riesgos e implicaciones sociales, y en la participación de nuevos actores en el desarrollo de la ciencia y la tecnología, entre otros factores. En este artículo se presentan los resultados del estudio sobre las funciones de un organismo con orígenes filantrópicos y no gubernamental que ha sido central en el desarrollo de los sistemas microelectromecánicos (MEMS) en México. Las funciones que se analizan han sido y son desarrolladas en las diferentes etapas del desarrollo de esta tecnología emergente en este país. Además de mostrar las funciones desempeñadas por este tipo de organismo, este texto se cuestiona sobre la modelización de las relaciones entre las diferentes entidades presentes en el desarrollo e instalación de nuevas tecnologías. En las conclusiones intentamos avanzar algunos elementos para tomar en cuenta estos organismos y enriquecer los estudios sociales sobre las nuevas ciencias y tecnologías. ABSTRACT: The emergence of new sciences and technologies come with new dynamics in the production, use and dissemination of new scientific and technological knowledge. These new dynamics are reflected in the reorganization of scientific activities, in creating or redirecting new topics in research, in the emergence of new concerns and debates about the risks and social implications, and the participation of new actors in the development of science and technology, among other factors. This article presents the results of the study on the functions of an organism with philanthropic and non-governmental sources that has been central to the development of microelectromechanical systems (MEMS) in Mexico. The functions have been discussed and are developed at different stages of development of this emerging technology in this country. In addition to showing the functions of such a body, this text is questioned on modeling the relationships between the various entities in the development and deployment of new technologies. In the conclusions we try moving some elements to take into account these organisms and enrich social studies on the new sciences and technologies.

Limitations and information needs for engineered nanomaterial-specific exposure estimation and scenarios: recommendations for improved reporting practices

The aim of this paper is to describe the process and challenges in building exposure scenarios for engineered nanomaterials (ENM), using an exposure scenario format similar to that used for the European Chemicals regulation (REACH). Over 60 exposure scenarios were developed based on information from publicly available sources (literature, books, and reports), publicly available exposure estimation models, occupational sampling campaign data from partnering institutions, and industrial partners regarding their own facilities. The primary focus was on carbon-based nanomaterials, nano-silver (nano-Ag) and nano-titanium dioxide (nano-TiO2), and included occupational and consumer uses of these materials with consideration of the associated environmental release. The process of building exposure scenarios illustrated the availability and limitations of existing information and exposure assessment tools for characterizing exposure to ENM, particularly as it relates to risk assessment. This article describes the gaps in the information reviewed, recommends future areas of ENM exposure research, and proposes types of information that should, at a minimum, be included when reporting the results of such research, so that the information is useful in a wider context.

The ADVANCE trial: clarifying the role of perindopril/indapamide fixed-dose combination in the reduction of cardiovascular and renal events in patients with diabetes mellitus.

Patients with type 2 diabetes mellitus exhibit a marked increase in cardiovascular and renal risk. A number of interventional trials have shown that these patients benefit greatly from aggressive BP lowering, especially when the drug regimen comprises an inhibitor of the renin-angiotensin system. The results of the placebo-controlled ADVANCE (Action in Diabetes and Vascular disease: PreterAx and DiamicroN MR Controlled Evaluation) trial, conducted in patients with type 2 diabetes, are exemplary in this respect. The systematic use of a fixed-dose combination containing the ACE inhibitor perindopril and the diuretic indapamide afforded substantial protection against cardiovascular mortality and myocardial infarction, while providing important renoprotection, reducing the development of micro- and macroalbuminuria, and allowing regression of nephropathy. The beneficial effects were obtained regardless of baseline BP and whether or not the patients were receiving antihypertensive therapy.

Do political factors matter in explaining under- and overweight outcomes in developing countries?

We construct a rich dataset covering 47 developing countries over the years 1990-2007, combining several micro and macro level data sources to explore the link between political factors and body mass index (BMI). We implement a heteroskedastic generalized ordered logit model allowing for different covariate effects across the BMI distribution and accounting for the unequal BMI dispersion by geographical area. We find that systems with democratic qualities are more likely to reduce under-weight, but increase overweight/obesity, whereas effective political competition does entail double-benefits in the form of reducing both under-weight and obesity. Our results are robust to the introduction of country fixed effects.

Treating tobacco use and dependence in clinical practice.

Physicians are in a unique position to advise smokers to quit by the ability to integrate the various aspects of nicotine dependence. This review provides an overview of the intervention strategies for smokers presented in a primary care setting. The strategies that are used for smoking cessation counselling differ according to the patient's readiness to quit. For smokers who do not intend to give up smoking, physicians should inform about tobacco use and the benefits of cessation. For smokers who are dissonant, physicians should use motivational strategies, such as discussing the barriers to successful cessation and their solutions. For smokers who are ready to quit, the physician should show strong support, help set a date to quit, prescribe pharmaceutical therapies for nicotine dependence, such as nicotine replacement therapy (i.e., gum, transdermal patch, nasal spray, mouth inhaler, lozenges, and micro and sublingual tablets) and/or bupropion (an atypical antidepressant thought to work by blocking the neural re-uptake of dopamine and/or noradrenaline), with instructions for use, and suggest behavioural strategies to prevent relapse. The efficacy of all of these pharmacotherapies is comparable, roughly doubling the cessation rates over control conditions.

Nanoparticles activate the NLR pyrin domain containing 3 (Nlrp3) inflammasome and cause pulmonary inflammation through release of IL-1α and IL-1β.

Nanoparticles are increasingly used in various fields, including biomedicine and electronics. One application utilizes the opacifying effect of nano-TiO(2), which is frequently used as pigment in cosmetics. Although TiO(2) is believed to be biologically inert, an emerging literature reports increased incidence of respiratory diseases in people exposed to TiO(2). Here, we show that nano-TiO(2) and nano-SiO(2), but not nano-ZnO, activate the NLR pyrin domain containing 3 (Nlrp3) inflammasome, leading to IL-1β release and in addition, induce the regulated release of IL-1α. Unlike other particulate Nlrp3 agonists, nano-TiO(2)-dependent-Nlrp3 activity does not require cytoskeleton-dependent phagocytosis and induces IL-1α/β secretion in nonphagocytic keratinocytes. Inhalation of nano-TiO(2) provokes lung inflammation which is strongly suppressed in IL-1R- and IL-1α-deficient mice. Thus, the inflammation caused by nano-TiO(2) in vivo is largely caused by the biological effect of IL-1α. The current use of nano-TiO(2) may present a health hazard due to its capacity to induce IL-1R signaling, a situation reminiscent of inflammation provoked by asbestos exposure.

Intracellular targeting of GLUT4 in transfected insulinoma cells: evidence for association with constitutively recycling vesicles distinct from synaptophysin and insulin vesicles.

In adipocytes and muscle cells, the GLUT4 glucose transporter isoform is present in intracellular vesicles which continuously recycle between an intracytoplasmic location and the plasma membrane. It is not clear whether the GLUT4-vesicles represent a specific kind of vesicle or resemble typical secretory granules or synaptic-like microvesicles. To approach this question, we expressed GLUT4 in the beta cell line RINm5F and determined its intracellular localization by subcellular fractionation and by immunofluorescence and immunoelectron microscopy. GLUT4 was not found in insulin granules but was associated with a subpopulation of smooth-surface vesicles present in the trans-Golgi region and in vesicular structures adjacent to the plasma membrane. In the trans-Golgi region, GLUT4 did not colocalize with synaptophysin or TGN38. Incubation of the cells with horseradish peroxidase (HRP) led to colocalization of HRP and GLUT4 in some endosomal structures adjacent to the plasma membrane and in occasional trans-Golgi region vesicles. When cells were incubated in the presence of Bafilomycin A, analysis by confocal microscopy revealed GLUT4 in numerous large spots present throughout the cytoplasm, many of which costained for TGN38 and synaptophysin. By immunoelectron microscopy, numerous endosomes were observed which stained strongly for GLUT4. Together our data demonstrate that ectopic expression of GLUT4 in insulinoma cells reveals the presence of a subset of vesicular structures distinct from synaptic-like vesicles and insulin secretory granules. Furthermore, they indicate that GLUT4 constitutively recycles between the plasma membrane and its intracellular location by an endocytic route also taken by TGN38 and synaptophysin.

Efficiency of coronary artery disease screening guidelines in asymptomatic and atypical chest pain type 2 diabetic patients

RESUME Objectifs. Évaluer la prévalence de maladie coronarienne chez les patients diabétiques de type 2 asymptomatiques ou avec angor atypique selon les recommandations américaines de l'American Diabetes Association et de l'American College of Cardiology. Méthodes. Cent cinquante-quatre patients diabétiques de type 2 asymptomatiques ou avec angor atypique et présentant au minimum 2 facteurs de risque cardio-vasculaires additionnels ont été dépistés par échocardiographie de stress (71%, n=109), scintigraphie myocardique de perfusion (26%, n=40) ou l'association des 2 examens (3%, n=5). Résultats. L'échocardiographie de stress s'est révélée positive chez 16 patients (14%) et 14 ont eu une coronarographie révélant des sténoses significatives chez 12 (86%). La scintigraphie myocardique de perfusion était positive chez 16 patients (36%). Huit patients ont eu une coronarographie et 4 (50%) présentaient des sténoses significatives. Au total, 31 patients (20%) ont montré des signes d'ischémie lors de l'examen non-invasif et 15 (10%) ont présenté des sténoses significatives à la coronarographie. Les facteurs prédictifs indépendants de la maladie coronarienne étaient le tabagisme (OR 6.5, p=0.05), la microalbuminurie (OR 3.9, p=0.03), ainsi que les souffles fémoraux (OR 17.1, p=0.008). Conclusions. En suivant les recommandations américaines, un patient sur cinq présentait une ischémie lors des examens non-invasifs, tandis que 1 sur 10 avait des sténoses significatives à la coronarographie. L'analyse multivariée suggère que des marqueurs des complications micro- et macro-vasculaires en combinaison avec des facteurs de risque cardio-vasculaire classiques pourraient améliorer le pouvoir diagnostic de ces recommandations. SUMMARY Aims. We evaluated the prevalence of coronary artery disease in asymptomatic and atypical chest pain type 2 diabetic patients according to the American Diabetes Association and American College of Cardiology guidelines. Methods. Asymptomatic or atypical chest pain type 2 diabetic patients (n=154), with at least two additional cardiovascular risk factors, were screened for coronary artery disease using stress echocardiography (71%, n=109), myocardial perfusion imaging (26%, n=40) or both (3%, n=5). Results. Stress echocardiography was positive in 16 patients (14%) and 14 had a coronary angiography, revealing significant stenoses in 12 (86%). Myocardial perfusion imaging was positive in 16 patients (36%). Eight patients underwent angiography and 4 (50%) presented significant stenoses. Overall, 31 patients (20%) demonstrated signs of ischemia on non-invasive tests and 15 (10%) presented significant stenoses on coronary angiography. Independent predictors of coronary artery disease were smoking (OR 6.5, p=0.05), microalbuminuria (OR 3.9, p=0.03) and femoral murmur (OR 17.1, p=0.008). Conclusions. Following the guidelines, one in five diabetic patient presented ischemia on noninvasive tests, while one in ten presented significant coronary stenoses. Multivariate analysis suggests that adding markers of micro- and macro-vascular complications to classical cardiovascular risk factors may enhance the diagnostic efficiency of the guidelines.