TRAIL/TRAIL Receptor System and Susceptibility to Multiple Sclerosis

The TNF-related apoptosis inducing ligand (TRAIL)/TRAIL receptor system participates in crucial steps in immune cell activation or differentiation. It is able to inhibit proliferation and activation of T cells and to induce apoptosis of neurons and oligodendrocytes, and seems to be implicated in autoimmune diseases. Thus, TRAIL and TRAIL receptor genes are potential candidates for involvement in susceptibility to multiple sclerosis (MS). To test whether single-nucleotide polymorphisms (SNPs) in the human genes encoding TRAIL, TRAILR-1, TRAILR-2, TRAILR-3 and TRAILR-4 are associated with MS susceptibility, we performed a candidate gene case-control study in the Spanish population. 59 SNPs in the TRAIL and TRAIL receptor genes were analysed in 628 MS patients and 660 controls, and validated in an additional cohort of 295 MS patients and 233 controls. Despite none of the SNPs withstood the highly conservative Bonferroni correction, three SNPs showing uncorrected p values<0.05 were successfully replicated: rs4894559 in TRAIL gene, p = 9.8×10−4, OR = 1.34; rs4872077, in TRAILR-1 gene, p = 0.005, OR = 1.72; and rs1001793 in TRAILR-2 gene, p = 0.012, OR = 0.84. The combination of the alleles G/T/A in these SNPs appears to be associated with a reduced risk of developing MS (p = 2.12×10−5, OR = 0.59). These results suggest that genes of the TRAIL/TRAIL receptor system exerts a genetic influence on MS

Short-term follow-up of chagasic patients after benznidazole treatment using multiple serological markers

<p>Abstract</p> <p>Background</p> <p>Conventional serological tests, using total soluble proteins or a cocktail of recombinant proteins from <it>T. cruzi </it>as antigens, are highly sensitive for Chagas disease diagnosis. This type of tests, however, does not seem to be reliable tools for short- and medium-term monitoring of the evolution of patients after antiparasitic treatment. The aim of the present study was to search for immunological markers that could be altered in the sera from Chagas disease patients after benznidazole treatment, and therefore have a potential predictive diagnostic value.</p> <p>Methods</p> <p>We analyzed the reactivity of sera from chagasic patients during different clinical phases of the disease against a series of immunodominant antigens, known as KMP11, PFR2, HSP70 and Tgp63. The reactivity of the sera from 46 adult Chronic Chagas disease patients living in a non-endemic country without vector transmission of <it>T. cruzi </it>(15 patients in the indeterminate stage, 16 in the cardiomiopathy stage and 16 in the digestive stage) and 22 control sera from non-infected subjects was analyzed. We also analyzed the response dynamics of sera from those patients who had been treated with benznidazole.</p> <p>Results</p> <p>Regardless of the stage of the sickness, the sera from chagasic patients reacted against KMP11, HSP70, PFR2 and Tgp63 recombinant proteins with statistical significance relative to the reactivity against the same antigens by the sera from healthy donors, patients with autoimmune diseases or patients suffering from tuberculosis, leprosy or malaria. Shortly after benznidazole treatment, a statistically significant decrease in reactivity against KMP11, HSP70 and PFR2 was observed (six or nine month). It was also observed that, following benznidazole treatment, the differential reactivity against these antigens co-relates with the clinical status of the patients.</p> <p>Conclusions</p> <p>The recombinant antigens KMP11, PFR2, Tgp63 and HSP70 are recognized by Chagas disease patients' sera at any clinical stage of the disease. Shortly after benznidazole treatment, a drop in reactivity against three of these antigens is produced in an antigen-specific manner. Most likely, analysis of the reactivity against these recombinant antigens may be useful for monitoring the effectiveness of benznidazole treatment.</p

Clinical presentation, causative drugs and outcome of patients with autoimmune features in two prospective DILI registries

Background & aims: Idiosyncratic drug-induced liver injury (DILI) with autoimmune features is a liver condition with laboratory and histological characteristics similar to those of idiopathic autoimmune hepatitis (AIH), which despite being increasingly re-ported, remains largely undefined. We aimed to describe in-depth the features of this entity in a large series of patients from two prospective DILI registries. Methods: DILI cases with autoimmune features collected in the Spanish DILI Registry and the Latin American DILI Network were compared with DILI patients without autoimmune features and with an independent cohort of patients with AIH. Results: Out of 1,426 patients with DILI, 33 cases with autoimmune features were identified. Female sex was more frequent in AIH patients than in the other groups (p= .001). DILI cases with autoimmune features had significantly longer time to onset (p< .001) and resolution time (p= .004) than those without autoimmune features. Interestingly, DILI patients with autoimmune features who relapsed exhibited significantly higher total bilirubin and transaminases at onset and absence of peripheral eosinophilia than those who did not relapse. The likelihood of relapse increased over time, from 17% at 6 months to 50% 4 years after biochemical normalization. Statins, nitrofurantoin and minocycline were the drugs most frequently associated with this phenotype. Conclusions: DILI with autoimmune features shows different clinical features than DILI patients lacking characteristics of autoimmunity. Higher transaminases and total bilirubin values with no eosinophilia at presentation increase the likelihood of relapse in DILI with autoimmune features. As the tendency to relapse increases over time, these patients will require long-term follow-up.Instituto de Salud Carlos III; Fondo Europeo de Desarrollo Regional— FEDER, Grant/Award Number: UMA18- FEDERJA-193, PI18/00901, PI19/00883 and PI21/01248; Consejería de Salud y Familia de la Junta de Andalucía, Grant/Award Number: P18-RT- 3364 and PI- 0310- 2018; Agencia Española del Medicamento; Sara Borrell, Grant/Award Number: CD20/00083; Rio Hortega, Grant/Award Number: CM21/00074; Garantía Juvenil, Grant/Award Number: SNGJ5Y6-09; Junta de Andalucía and European Social Fund; European Cooperation in Science and Technology; Universidad de Málaga/CBUA Funding for open access charge: Universidad de Málga / CBU

Imported malaria among African immigrants: is there still a relationship between developed countries and their ex-colonies?

© 2009 Millet et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Evaluations in the Moodle-Mediated Music Teaching-Learning Environment

This study presents the use of automated data analysis procedures in the teaching-learning process, mediated by telematics platforms. It is based on the application of the principles of virtual learning, the use of the Internet and the automation of data analysis of information collected in Moodle. The application of analysis procedures for the assessment of music competences is proposed based on the data collected in an exam administered at the end of the course. The sample of the study consists of 1327 students (n = 1327) in the first year of Compulsory Secondary Education in Spain and measures the level of acquisition of the key competences denominated “cultural and artistic”. The results are subjected to the K-means classification technique. This technique is used to obtain homogeneously distributed conglomerates which allow for an objective evaluation of the levels of acquisition of the key musical competences. © 2020, Springer Nature B.V

Parasitosis importadas en la población inmigrante en España

Background: Migration has contributed to the emergence of certain infectious diseases in host countries. In Spain the number of immigrants has increased exponentially in recent decades. The aim of this review is to identify and analyze the available information on imported parasitic diseases in immigrant population in our country. Methods: A scope review of original articles published on imported parasitic diseases between 1998 and 2012. Study populations from Latin America, Africa, Asia, Eastern Europe and individuals who are under the definition of an immigrant from International Organization for Migration were included. The literature search was performed in the Medline and MEDES-MEDicina databases. Results: A total of 51 descriptive studies were included in the analysis. Most immigrants attended at referral health facilities were originally from sub-Saharan Africa (between 16%-87%), followed by Latin America (13%-37%), while Asia was the region less represented (0.2%-8.8%). A considerable proportion (6.5-31%) of inmigrants that attended to referal units of tropical medicine or inmigrant health, and that were originally from Latin America, particularly those from Bolivia, are affected by the Chagas disease, and several cases of mother-to-child transmission have been registered in our country. Conclusion: Imported parasitosis is a frequent diagnosis among migrant population. This review highlight the impact that migration has had on the emergence of certain imported parasitic diseases, being Chagas disease the most paradigmatic example.Fundamentos: La migración ha contribuido a la emergencia de ciertas enfermedades infecciosas en los países receptores de inmigrantes. En España el número de inmigrantes ha crecido exponencialmente en las últimas décadas. El objetivo de esta revisión es identificar y analizar la información disponible sobre parasitosis importadas en población inmigrante en nuestro país. Métodos: Revisión de conjunto de artículos originales publicados sobre parasitosis importadas publicados entre 1998 y 2012. Se incluyeron trabajos realizados con poblaciones procedentes de Latinoamérica, África, Asia y Europa del Este o que cumplieran la definición de inmigrante de la Organización Internacional de Migraciones. La búsqueda bibliográfica se realizó en Medline y MEDES-MEDicina. Resultados: Se incluyó un total de 51 estudios descriptivos en el análisis. La mayor parte de los inmigrantes atendidos procedieron del África Subsahariana (16%-87% según estudios), seguidos de América Latina (13%-37%), siendo Asia la región menos representada (0,2%-8,8%). Destaca que el 6,5-31% de los inmigrantes atendidos en unidades de medicina tropical o de atención al inmigrante y procedentes de América Latina, en particular de Bolivia, están afectados por la enfermedad de Chagas y la existencia en nuestro país de casos de transmisión congénita de esta enfermedad. Conclusiones: Las parasitosis importadas son un diagnóstico frecuente entre la población inmigrante. Esta revisión pone de manifiesto el impacto que ha tenido la migración en la emergencia de ciertas enfermedades parasitarias importadas, siendo un ejemplo paradigmático la enfermedad de Chagas

Short-term follow-up of chagasic patients after benzonidazole treatment using multiple serological markers.

BACKGROUND: Conventional serological tests, using total soluble proteins or a cocktail of recombinant proteins from T. cruzi as antigens, are highly sensitive for Chagas disease diagnosis. This type of tests, however, does not seem to be reliable tools for short- and medium-term monitoring of the evolution of patients after antiparasitic treatment. The aim of the present study was to search for immunological markers that could be altered in the sera from Chagas disease patients after benznidazole treatment, and therefore have a potential predictive diagnostic value. METHODS: We analyzed the reactivity of sera from chagasic patients during different clinical phases of the disease against a series of immunodominant antigens, known as KMP11, PFR2, HSP70 and Tgp63. The reactivity of the sera from 46 adult Chronic Chagas disease patients living in a non-endemic country without vector transmission of T. cruzi (15 patients in the indeterminate stage, 16 in the cardiomiopathy stage and 16 in the digestive stage) and 22 control sera from non-infected subjects was analyzed. We also analyzed the response dynamics of sera from those patients who had been treated with benznidazole. RESULTS: Regardless of the stage of the sickness, the sera from chagasic patients reacted against KMP11, HSP70, PFR2 and Tgp63 recombinant proteins with statistical significance relative to the reactivity against the same antigens by the sera from healthy donors, patients with autoimmune diseases or patients suffering from tuberculosis, leprosy or malaria. Shortly after benznidazole treatment, a statistically significant decrease in reactivity against KMP11, HSP70 and PFR2 was observed (six or nine month). It was also observed that, following benznidazole treatment, the differential reactivity against these antigens co-relates with the clinical status of the patients. CONCLUSIONS: The recombinant antigens KMP11, PFR2, Tgp63 and HSP70 are recognized by Chagas disease patients' sera at any clinical stage of the disease. Shortly after benznidazole treatment, a drop in reactivity against three of these antigens is produced in an antigen-specific manner. Most likely, analysis of the reactivity against these recombinant antigens may be useful for monitoring the effectiveness of benznidazole treatment

Successful treatment with posaconazole of a patient with chronic Chagas disease and systemic lupus erythematosus

American Trypanosomiasis or Chagas disease (CD) is a neglected disease that affects Latin American people worldwide. Two old antiparasitic drugs, benznidazole and nifurtimox, are currently used for specific CD treatment with limited efficacy in chronic infections and frequent side effects. New drugs are needed for patients with chronic CD as well as for immunosuppressed patients, for whom the risk of reactivation is life-threatening. We describe a case of chronic CD and systemic lupus erythematosus (SLE) that required immunosuppression to control the autoimmune process. It was found that benznidazole induced a reduction, but not an elimination, of circulating Trypanosoma cruzi levels, whereas subsequent treatment with posaconazole led to a successful resolution of the infection, despite the maintenance of immunosuppressive therapy

Successful treatment with posaconazole of a patient with chronic Chagas disease and systemic lupus erythematosus

American Trypanosomiasis or Chagas disease (CD) is a neglected disease that affects Latin American people worldwide. Two old antiparasitic drugs, benznidazole and nifurtimox, are currently used for specific CD treatment with limited efficacy in chronic infections and frequent side effects. New drugs are needed for patients with chronic CD as well as for immunosuppressed patients, for whom the risk of reactivation is life-threatening. We describe a case of chronic CD and systemic lupus erythematosus (SLE) that required immunosuppression to control the autoimmune process. It was found that benznidazole induced a reduction, but not an elimination, of circulating Trypanosoma cruzi levels, whereas subsequent treatment with posaconazole led to a successful resolution of the infection, despite the maintenance of immunosuppressive therapy