ARAMIS: From systematic errors of NGS long reads to accurate assemblies.

NGS long-reads sequencing technologies (or third generation) such as Pacific BioSciences (PacBio) have revolutionized the sequencing field over the last decade improving multiple genomic applications like de novo genome assemblies. However, their error rate, mostly involving insertions and deletions (indels), is currently an important concern that requires special attention to be solved. Multiple algorithms are available to fix these sequencing errors using short reads (such as Illumina), although they require long processing times and some errors may persist. Here, we present Accurate long-Reads Assembly correction Method for Indel errorS (ARAMIS), the first NGS long-reads indels correction pipeline that combines several correction software in just one step using accurate short reads. As a proof OF concept, six organisms were selected based on their different GC content, size and genome complexity, and their PacBio-assembled genomes were corrected thoroughly by this pipeline. We found that the presence of systematic sequencing errors in long-reads PacBio sequences affecting homopolymeric regions, and that the type of indel error introduced during PacBio sequencing are related to the GC content of the organism. The lack of knowledge of this fact leads to the existence of numerous published studies where such errors have been found and should be resolved since they may contain incorrect biological information. ARAMIS yields better results with less computational resources needed than other correction tools and gives the possibility of detecting the nature of the found indel errors found and its distribution along the genome. The source code of ARAMIS is available at https://github.com/genomics-ngsCBMSO/ARAMIS.git.

Masquerade syndrome: An eye problem as a manifestation of a more sinister disease. / Síndrome de mascarada: un problema ocular como manifestación de un mal mayor.

A middle-aged man with cardiovascular risk factors, who suffered from a slight loss of unilateral vision for 6 months. After obtaining a diagnosis of diffuse choroiditis+papillitis within a probable masquerade syndrome, the patient was referred to outpatient Internal Medicine where this diagnosis was confirmed as an extended neoplastic disease.

Identification of proteins interacting with HSP70 mRNAs in Leishmania braziliensis.

HSP70 protein is involved in Leishmania differentiation, apoptosis, antimony-resistance and host-immune response. Therefore, this protein and the regulatory mechanisms of HSP70 gene expression are promising targets for therapeutic intervention against leishmaniasis. The regulation of mRNA expression in trypanosomatids operates mostly through the interaction of trans-acting proteins, and elements located in the untranslated regions of mRNAs. The aim of this work was to identify protein factors interacting specifically with the Leishmania braziliensis HSP70 mRNAs. Thus, the 5' UTR and the two types of 3' UTRs (UTR-I and UTR-II) from L. braziliensis HSP70 genes were used as baits in pull down assays using total protein extracts from parasites cultured at 26 or 35°C. The captured proteins were resolved by two-dimensional gel electrophoresis (2-DE) and identified by mass spectrometry (MS) analysis. As a result, 52 different proteins were identified based on their binding to the L. braziliensis HSP70-mRNAs. As expected, several of the identified proteins were related to RNA metabolism (27%) and translation process (7%). In addition, five hypothetical conserved proteins having motifs related with RNA interaction were also identified (9.6%). Nevertheless, unexpected proteins, apparently unrelated to the mRNA expression, were also identified. The biological significance of these and others L. braziliensis detected proteins, including the HSP70 itself, is discussed. BIOLOGICAL SIGNIFICANCE: For the first time, a riboproteomic analysis of the proteins interacting with the untranslated regions of the heat shock protein 70 (HSP70) mRNA from Leishmania braziliensis was carried out. This work provides new insights related to protein factors putatively involved in the regulation of HSP70 gene expression in L. braziliensis, and thereby, contributes to a better understanding of the parasite biology, and ultimately to the development of novel therapeutic interventions for controlling the important diseases caused by this parasite.

Influence of admission blood pressure on mortality in patients with acute decompensated heart failure.

OBJECTIVES: To determine the relationship between admission blood pressure (BP) and prognosis in patients hospitalized for acute decompensated heart failure (HF). BACKGROUND: The relationship between BP admission blood pressure and outcomes in decompensated HF is controversial. It has been suggested that this presentation may be a specific disorder, but their mechanisms and clinical relationships are poorly defined. METHODS: We evaluated the association between initial BP (systolic, diastolic and mean BP) with readmission and mortality, as well as potential interactions with age, clinical characteristics, renal function, left ventricular dysfunction, comorbidities and treatment. By using Cox regression models the association between each outcome and BP was tested. RESULTS: A total of 581 patients (77.5-years-old, range 51-100) were included. At admission, mean BP in quartiles was 77.09 mm Hg (53.3-85.0) (Q1); 91.46 mm Hg (85.0-96.7) (Q2); 103.41 mm Hg (96.7-109.9) (Q3) and 124.79 mm Hg (109.9-209.0) (Q4). Median duration of follow-up was 8 months [95% confidence interval (CI) 5.2-11.1]. Mortality was 15.5% (Q1), 9.2% (Q2), 12.6% (Q3) and 7.3% (Q4). Interquartile hazard ratio (95% CIs) for mortality was 0.40 (0.19-0.85) P=0.017. Body mass index (BMI) was higher in Q4 29.59 k/m2 than in Q1 28.25 k/m2 (P=0.018). There were no differences in age, clinical antecedents, renal function, comorbidities or severity of HF between groups. CONCLUSION: Higher mean BP at admission is associated with significantly lower mortality during follow-up, in patients hospitalized for HF. With the exception of BMI, positively correlated with blood pressure, this relationship is independent of other clinical factors and medications.

Bloqueo aurículo-ventricular completo como signo de afección cardíaca en paciente con esclerodermia / Complete atrioventricular block as sign of cardiac involvement in patient with scleroderma

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Favismo: una entidad a tener en cuenta en la zona mediterránea / Favism: a disease to keep in mind in the Mediterranean area

Se denomina favismo a la hemólisis aguda que se desarrolla tras la ingestión de habas o el polen de estas1. Los síntomas se desarrollan horas después de la ingestión, siendo comunes las náuseas, vómitos, malestar y vértigo. A estos síntomas le sigue una hemólisis. El favismo en el área mediterránea se debe a una variante de la glucosa-6-fosfato deshidrogenasa (G6PDH)1. Para su diagnóstico es fundamental una completa anamnesis, exploración física y la determinación de la actividad enzimática para la G6PDH. Los pacientes deben ser educados con unos consejos dietéticos y deben conocer la posibilidad de crisis hemolíticas agudas ante determinadas infecciones y exposición a determinados fármacos o tóxicos

Favism is called acute hemolysis that has developed after intake of fava beans or their pollen1. The symptoms develop hours after intake. The common symptoms are nausea, vomits, malaise and vertigo. Hemolysis follows these symptoms. Favism in the Mediterranean area is due to a variant of glucose-6-phosphate-dehydrogenase (G6PDH)1. A complete anamnesis, physical examination and measurement of enzyme activity for G6PDH are essential for its diagnosis. The patients should be educated with dietary advise and should know the possibility of acute hemolytic episodes when there are certain infections and exposure to certain drugs or toxics

Genomic organization and expression of the HSP70 locus in New and Old World Leishmania species.

Heat shock is believed to be a developmental inductor of differentiation in Leishmania. Furthermore, heat shock genes are extensively studied as gene models to decipher mechanisms of gene regulation in kinetoplastids. Here, we describe the organization and expression of the HSP70 loci in representative Leishmania species (L. infantum, L. major, L. tropica, L. mexicana, L. amazonensis and L. braziliensis). With the exception of L. braziliensis, the organization of the HSP70 loci was found to be well conserved among the other Leishmania species. Two types of genes, HSP70-I and HSP70-II, were found to be present in these Leishmania species except for L. braziliensis that lacks HSP70-II gene. Polymorphisms in the HSP70 locus allow the differentiation of the Old and New World species within the subgenus Leishmania. A notable discrepancy between our data and those of the L. major genome database in relation to the gene copy number composing the L. major HSP70 locus was revealed. The temperature-dependent accumulation of the HSP70-I mRNAs is also conserved among the different Leishmania species with the exception of L. braziliensis. In spite of these differences, analysis of the HSP70 synthesis indicated that the HSP70 mRNAs are also preferentially translated during heat shock in L. braziliensis.

Dolicoectasia basilar e ictus de repetición: dos nuevos casos / Basilar dolichoectasia and repeated strokes: two new cases

Introducción. La dolicoectasia vertebrobasilar (DEB) se define como la elongación, dilatación y tortuosidad de las arterias de la circulación cerebral posterior. La prevalencia es baja, al igual que la incidencia de ictus secundarios. El tratamiento es controvertido. Las manifestaciones clínicas dependen del territorio vascular afectado, tamaño del aneurisma y compresión de las estructuras adyacentes. Se manifiesta habitualmente por cuadros isquémicos focales del territorio posterior. Los avances en las técnicas de neuroimagen y su extensión a hospitales de nivel básico han incrementado el diagnóstico de DEB. Caso clínico. Presentamos dos casos de DEB manifestada como ictus de repetición. Se optó por el tratamiento antiagregante como opción terapéutica por motivos clínicos y sociales. Conclusión. La DEB es una rara entidad que se manifiesta más frecuentemente como cuadros isquémicos en personas de edad avanzada. La antiagregación plaquetaria puede ser una opción válida en estos pacientes

Introducction. Dolichoectasia vertebrobasilar (DEB) is defined as dilatation and winding of posterior brain circulation. The prevalence is low, as the same as incidence of secondary strokes. The treatment is controversial. The clinical manifestation depend on the vascular territory involved, aneurysm size and compression of adjacent structures. Often it is presented as strokes of vertebrobasilar territory. Advance in neuroimaging technique and the access to primary hospital have increased the diagnostic of DEB. Clinical cases. We report two cases of DEB its present as repeated strokes. Platelet antiagregation was select in basis to social and clinical reason. Conclusion. DEB is a rare entity. Frequently it present as strokes in elderly patients. Platelet antiagregation can be a reasonable therapeutic option

Immunohistological features of visceral leishmaniasis in BALB/c mice.

It has been reported that the level of protection provided by vaccines against murine visceral leishmaniasis (VL) is low and that progress in research on VL may be due to the lack of appropriate models to study protective immunity. We have analysed the immunohistological features occurring in BALB/c mice after intravenous administration of 10(3), 10(5) and 10(6) parasites of Leishmania infantum. Our results show that in all cases parasite administration leads to the establishment of infection and to the development of quantifiable immunohistological features which are dependent on the inoculum size. This study demonstrates that differences in the parasite challenge result in changes in the evolution of some of the parameters associated with the degree of the infection in the BALB/c model: level of anti-Leishmania antibodies, up-regulation of spleen arginase activity, balance between IFN-gamma and IL-10, extent of lymphoid follicle depletion in the splenic white pulp and ineffective development of hepatic granulomas. Also, and depending on the initial infectious inoculum, the absence of parasites in the bone marrow and the number of mature and empty type granulomas were parameters associated with protection. We think that in this model a challenge of the order of 10(5) parasites should prove useful for vaccine studies against VL.

Adjuvant guided polarization of the immune humoral response against a protective multicomponent antigenic protein (Q) from Leishmania infantum. A CpG + Q mix protects Balb/c mice from infection.

It has been shown that vaccination with three doses of the Leishmania infantum poly-protein Q containing five genetically fused antigenic determinants from the Lip2a, Lip2b, H2A and P0 proteins, mixed with BCG induces clearance of parasites in 9 out of 10 Leishmania infantum-infected Beagle dogs, in addition to clinical protection. In the present paper we analysed the immunogenic potential of the poly-protein Q and the specificity and polarization of the response against the antigenic determinants of Q when mixed with various adjuvants. The data showed that the Q protein had high intrinsic immunogenic potential and that it was able to induce a long-lasting IgG response. The IgM immunogenic potential of the poly-protein was mainly due to the LiP2a and LiP2b determinants, whereas the IgG immunogenic potential was mainly due to the LiP2a component. It was observed that the protein itself elicited a mixed IgG2a/IgG1 response and that the determinants of Q were endowed with different IgG2a/IgG1 potential. It was also observed that the adjuvants did not influence the intensity or specificity of the IgM response but that they modulated the intensity, the specificity and the polarization of the IgG response against the determinants of Q. CpG-ODN motifs or double-stranded DNA plasmids containing CpG motifs when mixed with Q induced a predominant IgG2a response mainly observed at early stages post-immunization. The data showed that a CpG + Q mix induced significant protection against L. infantum infection in Balb/c mice.

Leishmania infantum possesses a complex family of histone H2A genes: structural characterization and analysis of expression.

We have studied the genomic organization and transcription of the histone H2A genes in the protozoan parasite Leishmania infantum. In the parasite genome 2 gene clusters exist, each containing 3 H2A gene copies. Sequence analyses showed the existence of significant sequence divergence among the H2A genes, mainly in their 5'- and 3'-untranslated regions (UTRs). Also, the existence of allelic alternatives has been evidenced. Based on the divergence in the 3'UTR regions, we have defined 3 classes of H2A transcripts, which are present at different levels in L. infantum promastigotes. However, transcription of the 3 classes of H2A genes occurs at similar levels, as measured by nuclear run-on assays, indicating that their abundance is regulated post-transcriptionally. Also, differences in regulation were observed among the H2A transcripts: the levels of transcripts with 3'-UTR type I and type III are affected by growth phase whereas transcripts with 3'-UTR type II, that are barely detected, remain constant. It is likely that the complexity, in both gene organization and differential expression exhibited by the L. infantum H2A genes, is imposed by the nature of the post-transcriptional mechanisms of regulation operating in this parasite.

A Leishmania infantum multi-component antigenic protein mixed with live BCG confers protection to dogs experimentally infected with L. infantum.

The capacity of a quimeric protein, formed by the genetic fusion of five antigenic determinants from four Leishmania proteins, formulated with BCG, to protect dogs against Leishmania infantum infection is described. The data showed that after i.v. administration of 500,000 parasites of the L. infantum M/CAN/ES/96/BCN150 strain, zymodeme MON-1, the animals became infected as suggested by the humoral response against the parasite antigens. All control unvaccinated dogs had parasites in the lymph nodes at day 150 post-infection. One of these unvaccinated infected dog was parasite negative at day 634 behaving, thus, as resistant. In contrast, only 50% of the immunized dogs had parasites in the lymph nodes at day 150 post-infection. Four of these dogs became parasite negative by day 634 post-infection. The control animals developed at various times during the follow-up period clinical symptoms associated with Leishmaniasis. The control diseased dogs developed also in the liver and spleen some of the abnormal histological features associated with natural visceral Leishmaniasis. The immunized dogs, however, were not only normal at the clinical but also at the anatomo-pathological level. A positive delayed type hypersensitivity (DTH) response was observed in nine of the immunized protected dogs. The data indicated that Q+BCG confers 90% protection against infection and at least 90% protection at the clinical level.

Disección de aorta: a propósito de dos casos / Aortic disection: two cases review

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Alopecia aguda asociada a empiema por actinomices / Acute alopecia associated to empyema caused by actinomyces

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Aplasia pulmonar: un hallazgo infrecuente en adultos / Pulmonary hypoplasia: an infrecuent disease in adults

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Hipertensión arterial con alta variabilidad / Arterial hypertension with high variation

La hipertensión arterial esencial es la entidad que el clínico trata con más frecuencia en la práctica diaria.Los pacientes con gran variabilidad de la presión arterial (PA) representan un problema terapéutico y, con mayor frecuencia aún, un enigma diagnóstico. Se presenta un caso de enferma con crisis hipertensivas severas seguidas de baches hipotensivos en la cual, tras comprobarse la elevada variabilidad de su PA mediante medición ambulatoria de la presión arterial, se descubrió en el estudio posterior la existencia de una trombosis del seno transverso (AU)