Análisis coste-utilidad del modelo de unidad de terapia intravítrea (UTI) frente a la administración tradicional de terapia intravítrea / Cost-utility model of new intravítreous units vs. current patient journey model in Spain

Objetivo Comparar la efectividad y los costes de la implantación del Modelo de Unidad de Terapia Intravítrea (UTI), avalado por la Sociedad Española de Retina y Vítreo (SERV), Sociedad Española de Calidad Asistencial (SECA), Sociedad Española de Oftalmología (SEO) y Sociedad Española de Directivos Sanitarios (SEDISA) vs. el procedimiento habitual. Método Modelo de decisión analítico que compara una organización asistencial tipo UTI con cuatro escenarios de práctica habitual en España, en cuanto al resultado en la calidad de vida por pérdida de agudeza visual y la utilización de recursos. Se estimó la probabilidad, el coste y los años de vida ajustados por calidad (AVAC) para cada escenario planteado. Se realizó un análisis de sensibilidad univariante para cada uno de los parámetros empleados. Resultado Se observó que la implantación del modelo UTI mejora la calidad de vida de los pacientes y presenta un menor coste frente a la práctica habitual. Se produjo ahorro de costes y ganancia de AVAC. El análisis de sensibilidad mostró que el resultado no cambiaría de signo con la modificación de ninguna variable de partida. Conclusiones En las patologías oculares con indicación de tratamiento intravítreo, cualquier reducción en el tiempo que transcurre desde la sospecha diagnóstica hasta la primera inyección intravítrea disminuye la pérdida de agudeza visual. Así, actuar para acortar los tiempos sospecha-aguja es clave para mantener la visión funcional de los pacientes. La mejora de la eficiencia de los servicios de oftalmología que se organizan siguiendo el modelo UTI puede generar ahorros que varían entre los 175 € y 85 € por paciente atendido y año (AU)

Aim To compare the effectiveness and costs of the implementation of the intravitreal therapy unit model, endorsed by the SERV, SECA, SEO and SEDISA, compared to the usual procedure. Method Analytical decision model that compares an UTI-type healthcare organization with four usual practice scenarios in Spain, in terms of quality-of-life results due to loss of visual acuity and the use of resources. The probability, cost, and quality-adjusted life years (QALYs) were estimated for each scenario proposed. A univariate sensitivity analysis was performed for each of the parameters used in the model. Result The model showed that from any of the initial scenarios of the usual practice, transitioning to the UTI-type implementation improves the quality of life of patients and requires lower cost. UTI-type is dominant respect usual practice. The sensitivity analysis showed that the results would not change sign with the variation of any starting variable. Conclusions Shorten suspicion-needle times is key to maintaining functional vision in patients requiring intravitreal treatment. The UTI-type model seeks the efficiency of ophthalmology services and can produce savings that vary between €175 and €85 per patient attended per year (AU)

Cost-utility model of new intravitreous units vs. current patient journey model in Spain.

AIM: To compare the effectiveness and costs of the implementation of the Intravitreal Therapy Unit Model, endorsed by the SERV, SECA, SEO and SEDISA, compared to the usual procedure. METHOD: Analytical decision model that compares an UTI-type healthcare organization with 4 usual practice scenarios in Spain, in terms of quality-of-life results due to loss of visual acuity and the use of resources. The probability, cost, and quality-adjusted life years (QALYs) were estimated for each scenario proposed. A univariate sensitivity analysis was performed for each of the parameters used in the model. RESULT: The model showed that from any of the initial scenarios of the usual practice, transitioning to the UTI-type implementation improves the quality of life of patients and requires lower cost. UTI-type is dominant respect usual practice. The sensitivity analysis showed that the results would not change sign with the variation of any starting variable. CONCLUSIONS: Shorten suspicion-needle times is key to maintaining functional vision in patients requiring intravitreal treatment. The UTI-type model seeks the efficiency of ophthalmology services and can produce savings that vary between Є175 and Є85 per patient attended per year.

A combined exercise and cognitive training intervention induces fronto-cingulate cortical plasticity in first-episode psychosis patients.

OBJECTIVE: Schizophrenia (SZ) is characterized by neurobiological and associated cognitive and functional deficits, including pronounced cortical thinning, that lead to acute and long-term functional impairment. Research with older adults supports the role of non-pharmacological interventions, such as exercise (E) and cognitive training (CT), for cognitive impairments. This literature influenced the development of combined CT&E treatments for individuals with SZ. However, the impact of longer combined treatment duration (6 months) on neuroanatomy has yet to be explored in patients in the early course of the illness. The impact of adding exercise to cognitive training for key brain regions associated with higher-order cognition was examined here using magnetic resonance imaging (MRI) in first-episode psychosis (FEP) patients. METHODS: UCLA Aftercare Research Program patients with a recent first episode of schizophrenia were randomly assigned to either combined cognitive and exercise training (CT&E) (N = 20) or cognitive training alone (CT) (N = 17) intervention. Cortical thickness was measured longitudinally and analyzed for two regions of interest using FreeSurfer. RESULTS: Compared to patients in the CT group, those in the CT&E group demonstrated an increase in cortical thickness within the left anterior cingulate cortex over the six-month treatment period (ACC: F(1, 35) = 4.666, P < .04). Directional tendencies were similar in the left dorsolateral prefrontal cortex (DLPFC: F(1,35) = 4.132, P < .05). CONCLUSIONS: These findings suggest that exercise and cognitive training may synergistically increase fronto-cingulate cortical thickness to mitigate progressive neural atrophy in the early course of SZ. This combined intervention appears to be a valuable adjunct to standard pharmacologic treatment in FEP patients.

Aberrant perineuronal nets alter spinal circuits, impair motor function, and increase plasticity.

Perineuronal nets (PNNs) are a specialized extracellular matrix that have been extensively studied in the brain. Cortical PNNs are implicated in synaptic stabilization, plasticity inhibition, neuroprotection, and ionic buffering. However, the role of spinal PNNs, mainly found around motoneurons, is still unclear. Thus, the goal of this study is to elucidate the role of spinal PNNs on motor function and plasticity in both intact and spinal cord injured mice. We used transgenic mice lacking the cartilage link protein 1 (Crtl1 KO mice), which is implicated in PNN assembly. Crtl1 KO mice showed disorganized PNNs with an altered proportion of their components in both motor cortex and spinal cord. Behavioral and electrophysiological tests revealed motor impairments and hyperexcitability of spinal reflexes in Crtl1 KO compared to WT mice. These functional outcomes were accompanied by an increase in excitatory synapses around spinal motoneurons. Moreover, following spinal lesions of the corticospinal tract, Crtl1 KO mice showed increased contralateral sprouting compared to WT mice. Altogether, the lack of Crtl1 generates aberrant PNNs that alter excitatory synapses and change the physiological properties of motoneurons, overall altering spinal circuits and producing motor impairment. This disorganization generates a permissive scenario for contralateral axons to sprout after injury.

Persistent inflammation, immunosuppression and catabolism syndrome (PICS) in critically ill children is associated with clinical outcomes: a prospective longitudinal study.

BACKGROUND: Persistent inflammation, immunosuppression and catabolism syndrome (PICS) has been described in critically ill adults and may contribute to unfavourable outcomes. The present study aimed to describe and characterise PICS in critically ill children (PICS-ped) and to verify its association with clinical outcomes. METHODS: A prospective longitudinal study was conducted in a paediatric intensive care unit (PICU) with children aged between 3 months and 15 years. PICS-ped, based on adult definition, was described. PICS-ped was defined as PICU length of stay >14 days; C-reactive protein > 10.0 mg L-1 ; lymphocytes <25%; and any reduction of mid-upper arm circumference Z-score. Clinical, demographic, nutritional status, nutrition therapy parameters and clinical outcomes were assessed. Statistical analysis comprised Mann-Whitney and Fisher's chi-squared tests, as well as logistic and Cox regression. P < 0.05 was considered statistically significant. RESULTS: In total, 153 children were included, with a median age of 51.7 months (interquartile range 15.6-123.4 months), and 60.8% male. The mortality rate was 10.5%. The prevalence of PICS-ped was 4.6%. Days using vasoactive drugs and days using antibiotics were associated with PICS-ped. PICS-ped was associated with mortality in crude (odds ratio = 6.67; P = 0.013) and adjusted analysis (odds ratio = 7.14; P = 0.017). PICS-ped was also associated with PICU and hospital length of stay, as well as duration of mechanical ventilation. Similar results were found in a subset of critically ill children who required mechanical ventilation for more than 48 h. CONCLUSIONS: Children with PICS-ped required antibiotics or vasoactive drugs for a longer period. PICS-ped was associated with poor clinical outcomes in critically ill children. More studies are needed to properly define PICS-ped for this population.

Voluntary wheel running preserves lumbar perineuronal nets, enhances motor functions and prevents hyperreflexia after spinal cord injury.

Perineuronal nets (PNN) are a promising candidate to harness neural plasticity since their activity-dependent modulation allows to either stabilize the circuits or increase plasticity. Modulation of plasticity is the basis of rehabilitation strategies to reduce maladaptive plasticity after spinal cord injuries (SCI). Hence, it is important to understand how spinal PNN are affected after SCI and rehabilitation. Thus, this work aims to describe functional and PNN changes after thoracic SCI in mice, followed by different activity-dependent therapies: enriched environment, voluntary wheel and forced treadmill running. We found that the contusion provoked thermal hyperalgesia, hyperreflexia and locomotor impairment as measured by thermal plantar test, H wave recordings and the BMS score of locomotion, respectively. In the spinal cord, SCI reduced PNN density around lumbar motoneurons. In contrast, activity-based therapies increased motoneuron activity and reversed PNN decrease. The voluntary wheel group showed full preservation of PNN which also correlated with reduced hyperreflexia and better locomotor recovery. Furthermore, both voluntary wheel and treadmill running reduced hyperalgesia, but this finding was independent of lumbar PNN levels. In the brainstem sensory nuclei, SCI did not modify PNN whereas some activity-based therapies reduced them. The results of the present study highlight the impact of SCI on decreasing PNN at caudal segments of the spinal cord and the potential of physical activity-based therapies to reverse PNN disaggregation and to improve functional recovery. As modulating plasticity is crucial for restoring damaged neural circuits, regulating PNN by activity is an encouraging target to improve the outcome after injury.

Recommendations for eye care during the alarm state by the coronavirus disease pandemic COVID-19. / Recomendaciones para la atención oftalmológica durante el estado de alarma por la pandemia de enfermedad por coronavirus COVID-19.

OBJECTIVE: Minimize exposure to the SARS-CoV-2, reduce the chances of cross-transmission between patients and healthcare personnel, and prevent the development of postoperative complications from the management of patients with eye diseases during the 2019 coronavirus disease pandemic (COVID-19). METHODS: COVID-19 literature review and consensus establishment between different Spanish ophthalmology societies in order to provide guidelines and recommendations of maximum resources primarily conditioned by the state of alert, confinement and social distancing that occurs in Spain since March 16, 2020. RESULTS: The recommendations will promote the adoption of action and protection measures for eye care in outpatient clinics, surgical areas and hospitalization, for unconfirmed (asymptomatic and symptomatic) and confirmed COVID-19 patients. Measures must be adapted to the circumstances and availability of personal protective equipment in each of the centers and Autonomous Communities, which will be updated according to the pandemic phases and the measures adopted by the Spanish Government. CONCLUSIONS: During the COVID-19 pandemic, attention to the potential health risks to the population caused by coronavirus should prevail over the possible progression of the common eye diseases. Ophthalmologists and other eye care professionals must assume a possible progression of these diseases due to the impossibility of adequate patient follow-up.

Galectin-3 Is Associated with Cardiovascular Events in Post-Acute Coronary Syndrome Patients with Type-2 Diabetes.

INTRODUCTION: Type-2 diabetes mellitus (T2DM) is associated with early and severe atherosclerosis. However, few biomarkers can predict cardiovascular events in this population. METHODS: We followed 964 patients with coronary artery disease (CAD), assessing plasma levels of galectin-3, monocyte chemoattractant protein-1 (MCP-1), and N-terminal fragment of brain natriuretic peptide (NT-proBNP) at baseline. The secondary outcomes were acute ischemia and heart failure or death. The primary outcome was the combination of the secondary outcomes. RESULTS: Two hundred thirty-two patients had T2DM. Patients with T2DM showed higher MCP-1 (144 (113-195) vs. 133 (105-173) pg/mL, p = 0.006) and galectin-3 (8.3 (6.5-10.5) vs. 7.8 (5.9-9.8) ng/mL, p = 0.049) levels as compared to patients without diabetes. Median follow-up was 5.39 years (2.81-6.92). Galectin-3 levels were associated with increased risk of the primary outcome in T2DM patients (Hazard ratio (HR) 1.57 (1.07-2.30); p = 0.022), along with a history of cerebrovascular events. Treatment with clopidogrel was associated with lower risk. In contrast, NT-proBNP and MCP-1, but not galectin-3, were related to increased risk of the event in nondiabetic patients (HR 1.21 (1.04-1.42); p = 0.017 and HR 1.23 (1.05-1.44); p = 0.012, respectively), along with male sex and age. Galectin-3 was also the only biomarker associated with the development of acute ischemic events and heart failure or death in T2DM patients, while, in nondiabetics, MCP-1 and NT-proBNP, respectively, were related to these events. CONCLUSION: In CAD patients, galectin-3 plasma levels are associated with cardiovascular events in patients with T2DM, and MCP-1 and NT-proBNP in those without T2DM.

Resistive switching of silicon-silver thin film devices in flexible substrates.

Novel applications for memory devices demand nanoscale flexible structures. In particular, resistive switching (RS) devices are promising candidates for wearable and implantable technologies. Here, the Pt/Si/Ag/TiW metal-insulator-metal structure was fabricated and characterized on top of flexible substrates using a straightforward microfabrication process. We also showed that these substrates are compatible with sputtering deposition. RS was successfully achieved using both commercial cellulose cleanroom paper and bacterial cellulose, and polymer (PET) substrates. The bipolar switching behavior was observed for both flat and bent (under a radius of 3.5 mm) configurations. The observed phenomenon was explained by the formation/rupture of metallic Ag filaments in the otherwise insulating Si host layer.

A novel framework for biomedical entity sense induction.

BACKGROUND: Rapid advancements in biomedical research have accelerated the number of relevant electronic documents published online, ranging from scholarly articles to news, blogs, and user-generated social media content. Nevertheless, the vast amount of this information is poorly organized, making it difficult to navigate. Emerging technologies such as ontologies and knowledge bases (KBs) could help organize and track the information associated with biomedical research developments. A major challenge in the automatic construction of ontologies and KBs is the identification of words with its respective sense(s) from a free-text corpus. Word-sense induction (WSI) is a task to automatically induce the different senses of a target word in the different contexts. In the last two decades, there have been several efforts on WSI. However, few methods are effective in biomedicine and life sciences. METHODS: We developed a framework for biomedical entity sense induction using a mixture of natural language processing, supervised, and unsupervised learning methods with promising results. It is composed of three main steps: (1) a polysemy detection method to determine if a biomedical entity has many possible meanings; (2) a clustering quality index-based approach to predict the number of senses for the biomedical entity; and (3) a method to induce the concept(s) (i.e., senses) of the biomedical entity in a given context. RESULTS: To evaluate our framework, we used the well-known MSH WSD polysemic dataset that contains 203 annotated ambiguous biomedical entities, where each entity is linked to 2-5 concepts. Our polysemy detection method obtained an F-measure of 98%. Second, our approach for predicting the number of senses achieved an F-measure of 93%. Finally, we induced the concepts of the biomedical entities based on a clustering algorithm and then extracted the keywords of reach cluster to represent the concept. CONCLUSIONS: We have developed a framework for biomedical entity sense induction with promising results. Our study results can benefit a number of downstream applications, for example, help to resolve concept ambiguities when building Semantic Web KBs from biomedical text.

Wireless Vein and Artery Identifier for Laparoscopic Instruments / Identificador Inalámbrico de Venas y Arterias para Instrumentos Laparoscópicos

ABSTRACT This article presents an innovation on a conventional laparoscopic instrument, to which was added the automatic function to identify veins and arteries. It is proposed the use of a reflective-optical sensor with a specific work wavelength acting on blood vessels. The discrimination success between veins and arteries is achieved based on the range of difference between the light emitted and the light reflected. At the tip of a laparoscopic instrument was fitted a reflective-optical sensor composed of a LED and a light dependent resistor. In the upper part of the instrument an electronic control, processing and radio frequency transmitter module was fitted, which warns the surgeon and his assistants if the detected blood vessel is a vein or artery. The instrument was tested in vitro using whole human blood samples and in vivo on canine model blood vessels. With the innovation a low-cost support tool is achieved that could aid the surgeon when working on minimally invasive environments.

RESUMEN En este artículo se presenta una innovación realizada a un instrumento laparoscópico convencional, en la que se agrega la funcionalidad de identificación automática de venas y arterias. Se propone la utilización de un sensor óptico-reflexivo con longitud de onda específica, que actúa sobre los vasos sanguíneos. El éxito de discriminación entre venas y arterias se logra en función del rango de la diferencia entre la luz emitida versus la reflejada. A la punta de una pinza laparoscópica le fue adaptado un sensor óptico-reflexivo compuesto por un LED y una foto-resistencia. En la parte superior de la pinza, sobre el manipulador se adaptó un módulo electrónico de control, procesamiento y transmisión por radio frecuencia, el cual da aviso al cirujano y a sus asistentes si el vaso sanguíneo detectado es vena o arteria. El dispositivo fue probado in vitro utilizando muestras de sangre entera humana e in vivo sobre vasos sanguíneos de modelo canino. Con la innovación se logra una herramienta económica de apoyo para el cirujano que se desempeña en ambientes mínimamente invasivos.

High power and low critical current density spin transfer torque nano-oscillators using MgO barriers with intermediate thickness.

Reported steady-state microwave emission in magnetic tunnel junction (MTJ)-based spin transfer torque nano-oscillators (STNOs) relies mostly on very thin insulating barriers [resulting in a resistance × area product (R × A) of ~1 Ωµm2] that can sustain large current densities and thus trigger large orbit magnetic dynamics. Apart from the low R × A requirement, the role of the tunnel barrier in the dynamics has so far been largely overlooked, in comparison to the magnetic configuration of STNOs. In this report, STNOs with an in-plane magnetized homogeneous free layer configuration are used to probe the role of the tunnel barrier in the dynamics. In this type of STNOs, the RF modes are in the GHz region with integrated matched output powers (P out ) in the range of 1-40 nW. Here, P o u t values up to 200 nW are reported using thicker insulating barriers for junctions with R × A values ranging from 7.5 to 12.5 Ωµm2, without compromising the ability to trigger self-sustained oscillations and without any noticeable degradation of the signal linewidth (Γ). Furthermore, a decrease of two orders of magnitude in the critical current density for spin transfer torque induced dynamics (J STT ) was observed, without any further change in the magnetic configuration.

El marco analítico en la elaboración de recomendaciones del USPSTF / The analytic framework in USPSTF recommendations development

El planteamiento del marco analítico, y su representación gráfica, forma parte del abordaje integral para la realización de las revisiones sistemáticas que el US Preventive Services Task Force utiliza en el proceso de elaboración de sus recomendaciones. Se incluye como parte de la metodología para el desarrollo del plan de trabajo. Junto a las preguntas clave, establecen los pasos necesarios en la lógica clínica que deben ser demostrados para evaluar la eficacia y los daños de un servicio preventivo en Atención Primaria. El objetivo de un marco analítico es presentar clara y esquemáticamente las preguntas específicas que relacionan intervenciones y resultados y que deben ser contestadas por la revisión bibliográfica. Se describe una convención para su diseño respecto a los ítems, enlaces, símbolos y representación gráfica (AU)

The analytic framework and its graphic representation, takes part of the integral approach in the systematic reviews that the US Preventive Services Task Force develop in the process of developing their recommendations. It is included as part of the methodology for the process of the working plan. Together with the key questions, the analytic framework establishes the needed steps in the logical process that should be demonstrated in order to assess the efficacy and the harms of a preventive service in primary care. The objective of an analytic framework is to present clearly and schematically the specific questions that relate interventions and results and that should be answered through the bibliographic review. A convention for its design, items, links, symbols and graphic representation is described (AU)

Manual de trabajo del Grupo PrevInfad / Group PrevInfad workbook

Desde su creación, el Grupo PrevInfad ha trabajado con los objetivos de formular y mantener actualizadas las recomendaciones sobre actividades preventivas a realizar en la población infantil y adolescente española y mejorar la práctica clínica y promover la salud pública en el ámbito de la Atención Primaria. Las recomendaciones de PrevInfad van dirigidas principalmente a los pediatras de Atención Primaria, personal de enfermería y otros profesionales de la salud. En este trabajo presentamos una versión resumida del manual de trabajo del Grupo PrevInfad, que se ha actualizado recientemente. Para mayor detalle recomendamos a las personas interesadas consultar la versión íntegra, que se encuentra en la página web del grupo. Los métodos descritos están destinados a garantizar que las recomendaciones de PrevInfad sean metodológicamente sólidas, científicamente defendibles, reproducibles y bien documentadas (AU)

The working group PrevInfad has faced since its beginning the objectives of formulating and updating recommendations on preventive activities for Spanish children and adolescents, improving clinical practice and promoting public health in Primary Care. Previnfad recommendations address mainly to Primary Care paediatricians, nurses and other health professionals. In this paper, we present a resumed version of PrevInfad procedure manual, recently updated. We recommend to consult the complete version available in PrevInfad web site. The described methods are intended to ensure that the recommendations of PrevInfad are methodologically solid, scientifically defendable, reproducible and well documented (AU)

Association of ficolin-3 with abdominal aortic aneurysm presence and progression.

Essentials Abdominal aortic aneurysm (AAA) is asymptomatic and its evolution unpredictable. To find novel potential biomarkers of AAA, microvesicles are an excellent source of biomarkers. Ficolin-3 is increased in microvesicles obtained from activated platelets and AAA tissue. Increased ficolin-3 plasma levels are associated with AAA presence and progression. SUMMARY: Background Abdominal aortic aneurysm (AAA) patients are usually asymptomatic and AAA evolution is unpredictable. Ficolin-3, mainly synthesized by the liver, is a molecule of the lectin complement-activation pathway involved in AAA pathophysiology. Objectives To define extra-hepatic sources of ficolin-3 in AAA and investigate the role of ficolin-3 as a biomarker of the presence and progression of AAA. Methods Microvesicles (exosomes and microparticles) were isolated from culture-conditioned medium of ADP-activated platelets, as well as from AAA tissue-conditioned medium (thrombus and wall). Ficolin-3 levels were analyzed by western-blot, real-time PCR, immunohistochemistry and ELISA. Results Increased ficolin-3 levels were observed in microvesicles isolated from activated platelets. Similarly, microvesicles released from AAA tissue display increased ficolin-3 levels as compared with those from healthy tissue. Moreover, ficolin-3 mRNA levels in the AAA wall were greatly increased compared with healthy aortic walls. Immunohistochemistry of AAA tissue demonstrated increased ficolin-3, whereas little staining was present in healthy walls. Finally, increased ficolin-3 levels were observed in AAA patients' plasma (n = 478) compared with control plasma (n = 176), which persisted after adjustment for risk factors (adjusted odds ratio [OR], 5.29; 95% confidence interval [CI], 3.27, 8.57)]. Moreover, a positive association of ficolin-3 with aortic diameter (Rho, 0.25) and need for surgical repair was observed, also after adjustment for potential confounding factors (adjusted hazard ratio, 1.55; 95% CI, 1.11, 2.15). Conclusions In addition to its hepatic expression, ficolin-3 may be released into the extracellular medium via microvesicles, by both activated cells and pathological AAA tissue. Ficolin-3 plasma levels are associated with the presence and progression of AAA, suggesting its potential role as a biomarker of AAA.

Unipolar Nonvolatile Resistive Switching in Pt/MgO/Ta/Ru Structures Deposited by Magnetron Sputtering.

The recent realization of memristors, nanodevices exhibiting non-volatile resistive switching, has sparked tremendous interest for applications in fields such as nonvolatile memories. Here we report unipolar resistive switching in Pt/MgO/Ta/Ru structures, with an oxide barrier thickness of only 15 nm. No electroforming process was required to achieve resistive switching and an ohmic conduction mechanism is associated with the ON state. We observed an inverse dependence of the ON state resistance on the SET current compliance and average values of 1.61 V and 1.38 V for the SET and RESET voltages, respectively. We show the stability of the switching for over 40 cycles and a clear separation of the ON (10¹ Ω) and OFF (10² Ω) states during at least 104 s.

Expression of insulin receptor (IR) A and B isoforms, IGF-IR, and IR/IGF-IR hybrid receptors in vascular smooth muscle cells and their role in cell migration in atherosclerosis.

BACKGROUND: Abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) is a major contributor to the development of atherosclerotic process. In a previous work, we demonstrated that the insulin receptor isoform A (IRA) and its association with the insulin-like growth factor-I receptor (IGF-IR) confer a proliferative advantage to VSMCs. However, the role of IR and IGF-IR in VSMC migration remains poorly understood. METHODS: Wound healing assays were performed in VSMCs bearing IR (IRLoxP+/+ VSMCs), or not (IR-/- VSMCs), expressing IRA (IRA VSMCs) or expressing IRB (IRB VSMCs). To study the role of IR isoforms and IGF-IR in experimental atherosclerosis, we used ApoE-/- mice at 8, 12, 18 and 24 weeks of age. Finally, we analyzed the mRNA expression of total IR, IRB isoform, IGF-IR and IGFs by qRT-PCR in the medial layer of human aortas. RESULTS: IGF-I strongly induced migration of the four cell lines through IGF-IR. In contrast, insulin and IGF-II only caused a significant increase of IRA VSMC migration which might be favored by the formation of IRA/IGF-IR receptors. Additionally, a specific IGF-IR inhibitor, picropodophyllin, completely abolished insulin- and IGF-II-induced migration in IRB, but not in IRA VSMCs. A significant increase of IRA and IGF-IR, and VSMC migration were observed in fibrous plaques from 24-week-old ApoE-/- mice. Finally, we observed a marked increase of IGF-IR, IGF-I and IGF-II in media from fatty streaks as compared with both healthy aortas and fibrolipidic lesions, favoring the ability of medial VSMCs to migrate into the intima. CONCLUSIONS: Our data suggest that overexpression of IGF-IR or IRA isoform, as homodimers or as part of IRA/IGF-IR hybrid receptors, confers a stronger migratory capability to VSMCs as might occur in early stages of atherosclerotic process.