Development of a neuroprotective peptide that preserves survival pathways by preventing Kidins220/ARMS calpain processing induced by excitotoxicity.

Kinase D-interacting substrate of 220 kDa (Kidins220), also known as ankyrin repeat-rich membrane spanning (ARMS), has a central role in the coordination of receptor crosstalk and the integration of signaling pathways essential for neuronal differentiation, survival and function. This protein is a shared downstream effector for neurotrophin- and ephrin-receptors signaling that also interacts with the N-methyl-d-aspartate type of glutamate receptors (NMDARs). Failures in neurotrophic support and glutamate signaling are involved in pathologies related to excitotoxicity and/or neurodegeneration, where different components of these dynamic protein complexes result altered by a combination of mechanisms. In the case of Kidins220/ARMS, overactivation of NMDARs in excitotoxicity and cerebral ischemia triggers its downregulation, which contributes to neuronal death. This key role in neuronal life/death decisions encouraged us to investigate Kidins220/ARMS as a novel therapeutic target for neuroprotection. As the main mechanism of Kidins220/ARMS downregulation in excitotoxicity is proteolysis by calpain, we decided to develop cell-penetrating peptides (CPPs) that could result in neuroprotection by interference of this processing. To this aim, we first analyzed in detail Kidins220/ARMS cleavage produced in vitro and in vivo, identifying a major calpain processing site in its C-terminal region (between amino acids 1669 and 1670) within a sequence motif highly conserved in vertebrates. Then, we designed a 25-amino acids CPP (Tat-K) containing a short Kidins220/ARMS sequence enclosing the identified calpain site (amino acids 1668-1681) fused to the HIV-1 Tat protein basic domain, able to confer membrane permeability to attached cargoes. Transduction of cortical neurons with Tat-K reduced Kidins220/ARMS calpain processing in a dose- and time-dependent manner upon excitotoxic damage and allowed preservation of the activity of pERK1/2 and pCREB, signaling molecules central to neuronal survival and functioning. Importantly, these effects were associated to a significant increase in neuronal viability. This Kidins220/ARMS-derived peptide merits further research to develop novel neuroprotective therapies for excitotoxicity-associated pathologies.

Lysyl oxidase-like 2 (LOXL2) and E47 EMT factor: novel partners in E-cadherin repression and early metastasis colonization.

Epithelial-mesenchymal transition (EMT) has been associated with increased aggressiveness and acquisition of migratory properties providing tumor cells with the ability to invade into adjacent tissues. Downregulation of E-cadherin, a hallmark of EMT, is mediated by several transcription factors (EMT-TFs) that act also as EMT inducers, among them, Snail1 and the bHLH transcription factor E47. We previously described lysyl oxidase-like 2 (LOXL2), a member of the lysyl oxidase family, as a Snail1 regulator and EMT inducer. Here we show that LOXL2 is also an E47-interacting partner and functionally collaborates in the repression of E-cadherin promoter. Loss and gain of function analyses combined with in vivo studies in syngeneic breast cancer models demonstrate the participation of LOXL2 and E47 in tumor growth and their requirement for lung metastasis. Furthermore, LOXL2 and E47 contribute to early steps of metastatic colonization by cell and noncell autonomous functions regulating the recruitment of bone marrow progenitor cells to the lungs and by direct transcriptional regulation of fibronectin and cytokines TNFα, ANG-1 and GM-CSF. Moreover, fibronectin and GM-CSF proved to be necessary for LOXL2/E47-mediated modulation of tumor growth and lung metastasis.

Nuevos criterios ASAS para el diagnóstico de espondiloartritis. Diagnóstico de sacroileítis por resonancia magnética / New ASAS criteria for the diagnosis of spondyloarthritis: Diagnosing sacroiliitis by magnetic resonance imaging

La sacroileítis radiográfica ha formado parte del diagnóstico de las espondiloartropatías desde su inclusión en los criterios de Roma en 1961. Sin embargo, en la última década, la resonancia magnética (RM) ha demostrado ser más sensible para valorar las articulaciones sacroilíacas en los pacientes con sospecha de espondiloartritis y síntomas de sacroileítis, no solo para diagnosticarla, sino también para seguir la evolución de la enfermedad y el tratamiento de estos pacientes. El grupo The Assessment of SpondyloArthritis international Society (ASAS) desarrolló en el año 2009 unos criterios para clasificar y diagnosticar a los pacientes con espondiloartritis, entre los que destacaba la inclusión de un estudio de RM positivo para sacroileítis como criterio diagnóstico mayor. Este artículo incide en la parte radiológica de esta clasificación. Se describen e ilustran las diferentes alteraciones que podemos encontrarnos en los estudios de RM en pacientes con sacroileítis, resaltando las limitaciones y potenciales errores diagnósticos (AU)

Radiographic sacroiliitis has been included in the diagnostic criteria for spondyloarthropathies since the Rome criteria were defined in 1961. However, in the last ten years, magnetic resonance imaging (MRI) has proven more sensitive in the evaluation of the sacroiliac joints in patients with suspected spondyloarthritis and symptoms of sacroiliitis; MRI has proven its usefulness not only for diagnosis of this disease, but also for the follow-up of the disease and response to treatment in these patients. In 2009, The Assessment of SpondyloArthritis international Society (ASAS) developed a new set of criteria for classifying and diagnosing patients with spondyloarthritis; one important development with respect to previous classifications is the inclusion of MRI positive for sacroiliitis as a major diagnostic criterion. This article focuses on the radiologic part of the new classification. We describe and illustrate the different alterations that can be seen on MRI in patients with sacroiliitis, pointing out the limitations of the technique and diagnostic pitfalls (AU)

[New ASAS criteria for the diagnosis of spondyloarthritis: diagnosing sacroiliitis by magnetic resonance imaging]. / Nuevos criterios ASAS para el diagnóstico de espondiloartritis. Diagnóstico de sacroileítis por resonancia magnética.

Radiographic sacroiliitis has been included in the diagnostic criteria for spondyloarthropathies since the Rome criteria were defined in 1961. However, in the last ten years, magnetic resonance imaging (MRI) has proven more sensitive in the evaluation of the sacroiliac joints in patients with suspected spondyloarthritis and symptoms of sacroiliitis; MRI has proven its usefulness not only for diagnosis of this disease, but also for the follow-up of the disease and response to treatment in these patients. In 2009, The Assessment of SpondyloArthritis international Society (ASAS) developed a new set of criteria for classifying and diagnosing patients with spondyloarthritis; one important development with respect to previous classifications is the inclusion of MRI positive for sacroiliitis as a major diagnostic criterion. This article focuses on the radiologic part of the new classification. We describe and illustrate the different alterations that can be seen on MRI in patients with sacroiliitis, pointing out the limitations of the technique and diagnostic pitfalls.

Estudio de los receptores de somatostatina en una masa mesentérica poscirugía / No disponible

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Pulmonary actinomycosis with thoracic soft tissue mass: a rare onset form.

Actinomycosis is unusual, and rare especially when the lung and the thoracic wall are involved. It is more frequent in immunocompromised patient. US, CT, or MRI are imaging methods of diagnosis with high sensibility to recognise the disease and are able to the management. We point out a rare case in a normal teenager with thoracic abscess.

[Knowledge, attitude and practice in relation with HIV/AIDS infection in high-school and vocational training in Mieres]. / Conocimientos, actitudes y conductas en relación con la infección por el VIH/sida en estudiantes de bachillerato y formación profesional de Mieres.

OBJECTIVE: To find the students' level of knowledge, attitudes and conduct concerning HIV/AIDS. INTERVENTIONS: Data-gathering by means of a self-administered questionnaire. RESULTS: 450 students (60.8%), average age 17, took part. 52.9% answered questions on the disease correctly. 48.9% believed they had sufficient knowledge/information. More men than women thought they were well-informed. 89.6% said they would accept someone with AIDS in their class. 65% said they were worried about the possibility of being infected. 31.6% said they were sexually active. All of these affirmed that they knew of and took preventive measures. 83% said they always used a condom, the reason being to avoid pregnancy. 0.9% took intravenous drugs, but have never shared syringes. 100% knew that this protected them from infection. 42% (more men than women) believed that today's youth is changing its life-style because of AIDS. CONCLUSIONS: In spite of knowing the basic facts about HIV/AIDS, students have many mistaken ideas. They do not think that these facts have given rise to changes in their behaviour. These results could be useful for the design of a future health education intervention.