[Immunity against SARS-CoV-2: walking to the vaccination]. / Inmunidad frente a SARS-CoV-2: caminando hacia la vacunación.

The coronavirus are a wide group of viruses among that the SARS-CoV-2 is included (family Coronaviridae, subfamily Coronavirinae, genus Betacoronavirus and subgenus Sarbecovirus). Its main structural proteins are the membrane (M), the envelope (E), the nucleocapsid (N) and spike (S). The immune response to SARS-CoV-2 involves the cellular and the humoral sides, with neutralizing antibodies fundamentally directed against the S antigen. Although the seroprevalence data are frequently assumed as protection markers, no necessarily they are. In Spain, it is estimated that, to assure the herd immunity, at least four-fifths of the population should be immunoprotected. Due the high fatality rate of COVID-19, the acquisition of the protection only by the natural infection it not assumable and other measures as the mass immunization are required. Currently, there are several vaccine prototypes (including life virus, viral vectors, peptides and proteins and nucleic acid) in different phase of clinical evaluation. Foreseeably, some of these news vaccines would be soon commercially available. In this text, aspects related to these issues are reviewed.

From Beyond the Pale to the Pale Riders: The Emerging Association of Bacteria with Oral Cancer.

Oral cancer, predominantly oral squamous cell carcinoma (OSCC), is the eighth-most common cancer worldwide, with a 5-y survival rate <50%. There are numerous risk factors for oral cancer, among which periodontal disease is gaining increasing recognition. The creation of a sustained dysbiotic proinflammatory environment by periodontal bacteria may serve to functionally link periodontal disease and oral cancer. Moreover, traditional periodontal pathogens, such as Porphyromonas gingivalis, Fusobacterium nucleatum, and Treponema denticola, are among the species most frequently identified as being enriched in OSCC, and they possess a number of oncogenic properties. These organisms share the ability to attach and invade oral epithelial cells, and from there each undergoes its own unique molecular dialogue with the host epithelium, which ultimately converges on acquired phenotypes associated with cancer, including inhibition of apoptosis, increased proliferation, and activation of epithelial-to-mesenchymal transition leading to increased migration of epithelial cells. Additionally, emerging properties of structured bacterial communities may increase oncogenic potential, and consortia of P. gingivalis and F. nucleatum are synergistically pathogenic within in vivo oral cancer models. Interestingly, however, some species of oral streptococci can antagonize the phenotypes induced by P. gingivalis, indicating functionally specialized roles for bacteria in oncogenic communities. Transcriptomic data support the concept that functional, rather than compositional, properties of oral bacterial communities have more relevance to cancer development. Collectively, the evidence is consistent with a modified polymicrobial synergy and dysbiosis model for bacterial involvement in OSCC, with driver mutations generating a conducive microenvironment on the epithelial boundary, which becomes further dysbiotic by the synergistic action of bacterial communities.

KIDMED TEST; PREVALENCE OF LOW ADHERENCE TO THE MEDITERRANEAN DIET IN CHILDREN AND YOUNG; A SYSTEMATIC REVIEW.

INTRODUCTION: during the last decades, a quick and important modification of the dietary habits has been observed in the Mediterranean countries, especially among young people. Several authors have evaluated the pattern of adherence to the Mediterranean Diet in this group of population, by using the KIDMED test. OBJECTIVES: the purpose of this study was to evaluate the adherence to the Mediterranean Diet among children and adolescents by using the KIDMED test through a systematic review and meta-analysis. METHODS: PubMed database was accessed until January 2014. Only cross-sectional studies evaluating children and young people were included. A random effects model was considered. RESULTS: eighteen cross-sectional studies were included. The population age ranged from 2 to 25 years. The total sample included 24 067 people. The overall percentage of high adherence to the Mediterranean Diet was 10% (95% CI 0.07-0.13), while the low adhesion was 21% (IC 95% 0.14 to 0.27). In the low adherence group, further analyses were performed by defined subgroups, finding differences for the age of the population and the geographical area. CONCLUSION: the results obtained showed important differences between high and low adherence to the Mediterranean Diet levels, although successive subgroup analyzes were performed. There is a clear trend towards the abandonment of the Mediterranean lifestyle.

Introducción: en las últimas décadas se ha observado una modificación rápida e importante de los hábitos dietéticos en los países mediterráneos, especialmente entre los jóvenes. Varios autores han evaluado el patrón de adhesión a la Dieta Mediterránea en este grupo de población, mediante el uso de la prueba KIDMED. Objetivos: el objetivo de este estudio fue evaluar la adhesión a la Dieta Mediterránea entre los niños y adolescentes mediante el uso de la prueba KIDMED a través de una revisión sistemática y un metaanálisis. Métodos: la base de datos PubMed fue revisada hasta enero de 2014. Los estudios incluidos solo fueron los transversales que evaluaron a niños y a jóvenes. Se consideró un modelo de efectos aleatorios. Resultados: se incluyeron dieciocho estudios transversales. La edad de la población varió de 2 a 25 años. La muestra total incluyó 24.067 personas. El porcentaje global de alta adhesión a la Dieta Mediterránea fue del 10% (IC del 95%: 0,07 a 0,13), mientras que la baja adhesión fue del 21% (IC 95%: 0,14 a 0,27). Nuevos análisis por subgrupos definidos fueron realizados en el grupo de baja adhesión, encontrando diferencias para la edad de la población y para la zona geográfica. Conclusión: los resultados obtenidos mostraron diferencias importantes entre alta y baja adhesión a la Dieta Mediterránea, a pesar de los sucesivos análisis de subgrupos que se realizaron. Existe una clara tendencia hacia el abandono del estilo de vida mediterráneo.

KIDMED test; prevalence of low adherence to the Mediterranean Diet in children and young; a systematic review / Test KIDMED; prevalencia de la baja adhesión a la dieta mediterránea en niños y adolescentes; revisión sistemática

Introduction: during the last decades, a quick and important modification of the dietary habits has been observed in the Mediterranean countries, especially among young people. Several authors have evaluated the pattern of adherence to the Mediterranean Diet in this group of population, by using the KIDMED test. Objectives: the purpose of this study was to evaluate the adherence to the Mediterranean Diet among children and adolescents by using the KIDMED test through a systematic review and meta-analysis. Methods: PubMed database was accessed until January 2014. Only cross-sectional studies evaluating children and young people were included. A random effects model was considered. Results: eighteen cross-sectional studies were included. The population age ranged from 2 to 25 years. The total sample included 24 067 people. The overall percentage of high adherence to the Mediterranean Diet was 10% (95% CI 0.07-0.13), while the low adhesion was 21% (IC 95% 0.14 to 0.27). In the low adherence group, further analyses were performed by defined subgroups, finding differences for the age of the population and the geographical area. Conclusion: the results obtained showed important differences between high and low adherence to the Mediterranean Diet levels, although successive subgroup analyzes were performed. There is a clear trend towards the abandonment of the Mediterranean lifestyle (AU)

Introducción: en las últimas décadas se ha observado una modificación rápida e importante de los hábitos dietéticos en los países mediterráneos, especialmente entre los jóvenes. Varios autores han evaluado el patrón de adhesión a la Dieta Mediterránea en este grupo de población, mediante el uso de la prueba KIDMED. Objetivos: el objetivo de este estudio fue evaluar la adhesión a la Dieta Mediterránea entre los niños y adolescentes mediante el uso de la prueba KIDMED a través de una revisión sistemática y un metaanálisis. Métodos: la base de datos PubMed fue revisada hasta enero de 2014. Los estudios incluidos solo fueron los transversales que evaluaron a niños y a jóvenes. Se consideró un modelo de efectos aleatorios. Resultados: se incluyeron dieciocho estudios transversales. La edad de la población varió de 2 a 25 años. La muestra total incluyó 24.067 personas. El porcentaje global de alta adhesión a la Dieta Mediterránea fue del 10% (IC del 95%: 0,07 a 0,13), mientras que la baja adhesión fue del 21% (IC 95%: 0,14 a 0,27). Nuevos análisis por subgrupos definidos fueron realizados en el grupo de baja adhesión, encontrando diferencias para la edad de la población y para la zona geográfica. Conclusión: los resultados obtenidos mostraron diferencias importantes entre alta y baja adhesión a la Dieta Mediterránea, a pesar de los sucesivos análisis de subgrupos que se realizaron. Existe una clara tendencia hacia el abandono del estilo de vida mediterráneo (AU)

Vasculitis necrosante inducida por cocaína / Necrotizing vasculitis induced by cocaine

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Pyoderma gangrenosum and Wegener granulomatosis-like syndrome induced by cocaine.

Cocaine abuse is associated with various skin and rheumatological diseases that mimic primary autoimmune diseases, including retiform purpura with involvement of the ears, cocaine-induced midline destructive lesions (CIMDL), and eruptive pyoderma gangrenosum (PG). Previous reports have suggested the use of perinuclear antineutrophil cytoplasmic antibodies (pANCA) with specificity against human neutrophil elastase (HNE) to differentiate these cocaine-induced diseases from primary autoimmune diseases. We describe a case of a 54-year-old woman with a history of cocaine abuse, who had PG lesions on her legs with accompanying CIMDL and lung lesions similar to those seen in Wegener granulomatosis. Detection of HNE-positive pANCA, and improvement or clinical recurrence after cessation or consumption of cocaine, respectively, were key to differentiating this presentation from primary autoimmune disease.

Sodium tungstate modulates ATM function upon DNA damage.

Both radiotherapy and most effective chemotherapeutic agents induce different types of DNA damage. Here we show that tungstate modulates cell response to DNA damaging agents. Cells treated with tungstate were more sensitive to etoposide, phleomycin and ionizing radiation (IR), all of which induce DNA double-strand breaks (DSBs). Tungstate also modulated the activation of the central DSB signalling kinase, ATM, in response to these agents. These effects required the functionality of the Mre11-Nbs1-Rad50 (MRN) complex and were mimicked by the inhibition of PP2A phosphatase. Therefore, tungstate may have adjuvant activity when combined with DNA-damaging agents in the treatment of several malignancies.

Anti-diabetic and anti-obesity agent sodium tungstate enhances GCN pathway activation through Glc7p inhibition.

Tungstate counteracts diabetes and obesity in animal models, but its molecular mechanisms remain elusive. Our Saccharomyces cerevisiae-based approach has found that tungstate alleviated the growth defect induced by nutrient stress and enhanced the activation of the GCN pathway. Tungstate relieved the sensitivity to starvation of a gcn2-507 yeast hypomorphic mutant, indicating that tungstate modulated the GCN pathway downstream of Gcn2p. Interestingly, tungstate inhibited Glc7p and PP1 phosphatase activity, both negative regulators of the GCN pathway in yeast and humans, respectively. Accordingly, overexpression of a dominant-negative Glc7p mutant in yeast mimicked tungstate effects. Therefore tungstate alleviates nutrient stress in yeast by in vivo inhibition of Glc7p. These data uncover a potential role for tungstate in the treatment of PP1 and GCN related diseases.

[Description of an arthroscopic and percutaneous technique to repair posterolateral corner knee lesions]. / Descripción de una técnica artroscópica y percutánea para la reparación de lesiones de esquina posterolateral de rodilla.

Posterolateral corner knee lesions are infrequent and very disabling. They usually occur with other ligament lesions, so historically different techniques have been used to reconstruct this kind of lesions. Most of them involve open surgery, with the Clancy procedure as one of the most popular ones. After thorough preoperative planning taking into account the patient's activities, we propose a new arthroscopic and percutaneous technique based on Clancy's procedure, using a calcaneal tendon or quadriceps allograft.

Impaired anti-pneumococcal polysaccharide antibody production and invasive pneumococcal infection following heart transplantation.

An increased risk of invasive pneumococcal infection has been described among adult heart transplant (HT) recipients. Vaccination has been recommended before HT but the appropriate time for revaccination is not known. In a preliminary analysis of a prospective study involving a cohort of 32 HT recipients receiving daclizumab and triple immunosuppresion therapy, a progressive decline in pneumococcal polysaccharide antibody (anti-PPS) levels was observed during the first year after HT. One of the patients who was found to have a decrease in the levels of anti-PPS developed severe pneumococcal meningitis 20 months after HT. Before HT he had received non-conjugated 23-valent pneumococcal vaccine and showed a normal post-immunization anti-PPS production. The data suggest that long-term immunologic monitoring might be useful to recognize impairment of antibody responses under immunosuppressive therapy in HT.

FK506 sensitizes mammalian cells to high osmolarity by modulating p38 MAP kinase activation.

The immunosuppressants tacrolimus (FK506) and cyclosporin A (CsA) have increased the survival rates in organ transplantation. Both drugs inhibit the protein phosphatase calcineurin (CaN) in activated T cells, exhibiting similar side-effects. Diabetes is observed more often in FK506 than CsA therapy, probably due to inhibition of new molecular targets other than CaN. We studied FK506 toxicity in mammalian cells. FK506, but not CsA, regulated p38 activation by osmotic stress, and decreased viability in osmostressed cells. In addition, FK506 treatment strongly increased the phosphorylation of the eukaryotic initiation factor-2alpha (eIF-2alpha) subunit. eIF-2alpha phosphorylation, p38 inhibition and cell lethality were relieved by addition of excess amino acids to the medium, suggesting that amino acid availability mediated FK506 toxicity. Therefore, these FK506-dependent responses could be relevant to the non-therapeutic effects of FK506 therapy.

[Anti-ribosomal antibodies in systemic lupus erythematosus]. / Anticuerpos antirribosomales en le lupus eritematoso sistémico.

OBJECTIVES: To compare indirect immunofluorescence (IIF) with immunoblotting (IB) in the detection of antiribosomal antibodies (anti-P Ab) in patients with systemic lupus erythematosus (SLE) and to investigate the possible association between anti-P Ab with serological and clinical findings in SLE, particularly with neurological manifestations. METHODS: Serum specimens from 44 SLE patients and 10 healthy subjects were investigated for anti-P Ab using IB and IIF in rat triple substrate and HEp-2 cells. In SLE patients measurements were made of antinuclear Ab, anti-DNA ds Ab, anti-Sm Ab, anti-U1RNP Ab, anti-Ro Ab, and anti-La Ab. Clinical manifestations of SLE were collected retrospectively when the serological investigation was made. RESULTS: Of the 44 serum specimens tested, 9 showed a ribosomal pattern with triple rat substrate; 8 of them were IB positive (sensitivity 88%; specificity 97%); 12 serum specimens showed a ribosomal pattern with HEp-2 cells by the IIF technique, 9 were positive by IB (sensitivity 100%; specificity 91%). All ten healthy subjects were negative both with IIF and with IB. The nine patients with anti-P Ab in IB (20.45%) had anti-Ro Ab (55% vs. 37%), Anti-Sm Ab (33% vs. 22%, and U1RNP Ab (33% vs. 20%) more frequently than the 35 negative cases. Central nervous system disease (33 vs. 14%), and particularly seizures (33% vs. 5%) and psychosis (22% vs. 8%) were more common in cases with anti-P Ab, but as with serological associations, none of them reached a statistical signification. CONCLUSIONS: IIF with both rat triple substrate and HEp-2 cells is useful for the presumptive diagnosis of anti-P Ab in patients diagnosed with SLE. No significant serological or clinical association was found in patients with anti-P Ab, although neurological disease was more common in these cases.