Mortality and cardiovascular risk in vasculitis ANCA. Importance of hypertension and renal function. Experience from southern Spain.

BACKGROUND: Cardiovascular disease (CVD) is one of the principal causes of death in antineutrophil cytoplasmic antibody-(ANCA)-associated vasculitis (AAV). OBJECTIVES: To evaluate the mortality and it's causes and CVD and its vascular risk factors (VRFs) in AAV patients in Andalusia. METHODS: A multicenter cohort of 220 AAV patients followed-up from 1979 until June 2020 was studied in Andalussia, south of Spain. The information, including socio-demographic and clinical data was recorded retrospectively through chart review. Data was analysed using Chi2, ANOVA and Cox proportional hazards regresion as uni and multivariate test with a 95% confidence interval (CI). RESULTS: During a mean ± standard deviation follow-up of 96.79 ± 75.83 months, 51 patients died and 30 presented at least one CVE. Independent prognostic factors of mortality were age (HR 1.083, p=0.001) and baseline creatinine (HR 4.41, p=0.01). Independent prognostic factors of CVE were age [hazard ratio (HR) 1.042, p=0.005] and the presence of hypertension (HTN) six months after diagnosis (HR 4.641, p=0.01). HTN, diabetes and renal failure, all of these important VRFs, are more prevalent in AAV patients than it is described in matched general population. CONCLUSIONS: Age and baseline renal function, but not CVEs, are predictors of mortality and age and early HTN are independent predictors for having a CVE. CVD screening in AAV patients is demanded.

KI effects on corrosion inhibition for 1018 steel in acid media using Medicago sativa.

Medicago sativa (M. sativa) extract is a safe and eco-friendly corrosion inhibitor of 1018 steel in acid media. The inhibitor reached a maximum efficiency of 85% by using 500 ppm. In this work, we study the use of KI as an add-on to increase the inhibition efficiency of M. sativa, as well as making the natural inhibitor competitive with the commercial ones. We evaluated the effect of halide ions through the variation of different concentrations of KI and its synergy with the extract of M. sativa as a corrosion inhibitor of carbon steel in 0.5 M sulfuric acid and at different temperatures. The results were obtained through electrochemical techniques such as electrochemical impedance spectroscopy (EIS), potentiodynamic polarization (PDP) curves, and weight loss gravimetric technique. It was found that halide ions increase the inhibition efficiency of M. sativa from 85 to 95% when 5 mM concentration of KI was used. The efficiency of the inhibition increases proportionally with the immersion time but reduces when the temperature increases. The addition of iodide ions (I-) revealed that it exerts a synergistic effect on the inhibition of corrosion with the extract of M. sativa. However, when studying the metal surface using a scanning electron microscope, pitting corrosion was found.

Mutational analysis of Rox1, a DNA-bending repressor of hypoxic genes in Saccharomyces cerevisiae.

Rox1 is a repressor of the hypoxic genes of Saccharomyces cerevisiae. It binds to a specific hypoxic consensus sequence in the upstream region of these genes and represses transcription in conjunction with the general repression complex Tup1-Ssn6. In this study, we demonstrated that the first 100 amino acids comprising the HMG domain of Rox1 were responsible for DNA binding and that when bound, Rox1 bent DNA at an angle of 90 degrees. A mutational analysis resulted in the isolation of seven missense mutations, all located within the HMG domain, that caused loss of DNA binding. The effect of these mutations on the structure of Rox1 was evaluated on the basis of the homology between Rox1 and the human male sex-determining protein SRY, for which a structural model is available. The failure to isolate missense mutations in the carboxy-terminal three-quarters of the protein prompted a deletion analysis of this region. The results suggested that this region was responsible for the repression function of Rox1 and that the repression information was redundant. This hypothesis was confirmed by using a set of fusions between sequences encoding the GAL4 DNA-binding domain and portions of ROX1. Those fusions containing either the entire carboxy-terminal region or either half of it were capable of repression. Repression by selected fusions was demonstrated to be dependent on Ssn6.

The transcription factor PLA-1/SKN-1A is expressed in human placenta and regulates the placental lactogen-3 gene expression.

Here we report the selective expression of two POU transcription factor genes, PLA-1 and OCT-1, in human placenta and choriocarcinoma cell lines JAR, JEG-3 and BeWo. Pla-1 protein binds to a POU-consensus DNA sequence in the human placental lactogen-3 (PL-3) promoter and it is capable of trans-activating its transcription up to 18-fold. Other tissue-specific or ubiquitous POU transcription factors such as Pit-1/GHF-1 or Oct-1 showed none or low levels of trans-activation of the PL-3 promoter. In addition, we identified an unique and highly charged region in the N-terminal portion of Pla-1 protein required for full trans-activation of the PL-3 promoter.

Rox3 and Rts1 function in the global stress response pathway in baker's yeast.

Yeast respond to a variety of stresses through a global stress response that is mediated by a number of signal transduction pathways and the cis-acting STRE DNA sequence. The CYC7 gene, encoding iso-2-cytochrome c, has been demonstrated to respond to heat shock, glucose starvation, approach-to-stationary phase, and, as we demonstrate here, to osmotic stress. This response was delayed in a the hog1-delta 1 strain implicating the Hog1 mitogen-activated protein kinase cascade, a known component of the global stress response. Deletion analysis of the CYC7 regulatory region suggested that three STRE elements were each capable of inducing the stress response. Mutations in the ROX3 gene prevented CYC7 RNA accumulation during heat shock and osmotic stress. ROX3 RNA levels were shown to be induced by stress through a novel regulatory element. A selection for high-copy suppressors of a ROX3 temperature-sensitive allele resulted in the isolation of RTS1, encoding a protein with homology to the B' regulatory subunit of protein phosphatase 2A0. Deletion of RTS1 caused temperature and osmotic sensitivity and increased accumulation of CYC7 RNA under all conditions. Over-expression of this gene caused increased CYC7 RNA accumulation in rox3 mutants but not in wild-type cells.

Codon usage in Kluyveromyces lactis and in yeast cytochrome c-encoding genes.

Codon usage (CU) in Kluyveromyces lactis has been studied. Comparison of CU in highly and lowly expressed genes reveals the existence of 21 optimal codons; 18 of them are also optimal in other yeasts like Saccharomyces cerevisiae or Candida albicans. Codon bias index (CBI) values have been recalculated with reference to the assignment of optimal codons in K. lactis and compared to those previously reported in the literature taking as reference the optimal codons from S. cerevisiae. A new index, the intrinsic codon deviation index (ICDI), is proposed to estimate codon bias of genes from species in which optimal codons are not known; its correlation with other index values, like CBI or effective number of codons (Nc), is high. A comparative analysis of CU in six cytochrome-c-encoding genes (CYC) from five yeasts is also presented and the differences found in the codon bias of these genes are discussed in relation to the metabolic type to which the corresponding yeasts belong. Codon bias in the CYC from K. lactis and S. cerevisiae is correlated to mRNA levels.

Differential scanning calorimetry investigations on LPS and free lipids A of the bacterial cell wall.

Differential scanning calorimetry (DSC) was used to investigate the thermal stability and behaviour of the lipopolysaccharides (LPS) of the outer membrane of Gram-negative bacteria and their lipid portion. DSC curves of LPS show thermal features between 200 and 129 degrees C (depolymerization) and between -13 and -36 degrees C (cooling phase transition). Both effects were related to the relative strength of the linkage types in the O-chain structure and to their capacity for intermolecular hydrogen bonding. DSC curves of lipids A show endotherm peaks between 40 and 24 degrees C, around 15 degrees C and between -23 and -4 degrees C. Based on these effects, strong differences in thermal behaviour can be observed between that of Brucella and Vibrio cholerae on the one hand, and that of Escherichia coli and Shigella flexneri on the other. Fluidity of the acyl chains and lyotropism, which are important parameters in expression of biological activities, are discussed using the above data. To explain some properties, fluidity could be related to the temperature of the gel<==>liquid crystalline (beta<==>alpha) phase transition, which occurs at physiological temperature. Nevertheless, fluidity could be related to temperature of the previous thermal effect (between 6 and 20 degrees C), for which a softening or partial melting of the sample has been evidenced. The thermal effect measured between -23 degrees C and -4 degrees C indicates a greatly reduced water concentration of lipid A from Brucella, thus explaining its early fusion process and its activity by means of hydrophobic interactions.

Evaluation of six serological tests in diagnosis and postoperative control of pulmonary hydatid disease patients.

Latex agglutination (LA), passive hemagglutination (PHA), immunoelectrophoresis (IEP) and specific IgE, IgM, IgG enzyme-linked immunosorbent assay (ELISA) tests for diagnosis and postoperative follow-up of 79 patients with surgically confirmed pulmonary hydatidosis were evaluated. Specific IgG ELISA was the most sensitive test (83.5%) and the least sensitive tests were specific IgE ELISA (44.3%) and IEP (50.6%). The specificity obtained for all the serologic test was above 97% in all cases. The greatest number of false positives in all tests (except IEP) occurred in patients with Taenia saginata and Taenia solium cysticerci infestations and in patients with lymphoma and leukemia. Specific IgG ELISA demonstrated the highest negative predictive value (93.8%). No statistically significant differences (p > 0.050) were found in the sensitivity of the tests when patients with only one cyst and patients with various cysts were compared. Considering only the patients without relapse, the percentage of seropositive patients increased in all tests at 1 and 3 months after surgery. After that time the percentage of seropositive patients decreased. At 48 months after surgery all patients without relapse became negative in IEP, specific IgE ELISA, and specific IgM ELISA. The antibody titers in all seropositive patients increased during the 3 months after surgery. From these 3 months onward, antibody levels decreased in all serologic tests studied in the group of patients without relapse. The patients who had relapses during the first year after surgery presented persistently elevated antibody titers in all postoperative sera. The antibody titers of the patients who relapsed between the third and fourth years after surgery decreased progressively the third month after surgery, and increased in the serum obtained at the moment of relapse diagnosis. Our results show that persistence of elevated antibody titers in patients with pulmonary hydatidosis in the year after surgery or titer increase after a progressive decrease are indicative of relapse or reinfection.

PICDI, a simple program for codon bias calculation.

PICDI is a very simple program designed to calculate the Intrinsic Codon Deviation Index (ICDI). The program is available in Macintosh as well a PC format. Requirements for correct input of the sequences have been kept to a minimum and the analysis of sequences up to 2000 codons is very quick. The ICDI is very useful for estimation of codon bias of genes from species in which optimal codons are not known. The availability of a computer program for its calculation will increase its usefulness in the fields of Molecular Biology and Biotechnology.

Identification of species of Brucella using Fourier transform infrared spectroscopy.

Fourier transform infrared spectroscopy (FTIR) is a technique that has been used over the years in chemical analysis for the identification of substances and is one that may be applied to the characterisation of microorganisms. The marked tendency of Brucella towards variation in the smooth rough phase, together with the laboriousness and risk involved in the methods used in their identification, make their classification difficult. We studied the type strains of the different species and biovars of Brucella and 11 isolates of human origin of Brucella melitensis, six corresponding to biovar 1, one to biovar 2 and five to biovar 3. The results of linear discriminant analysis performed using the data provide an above 95% likelihood of correct classification, over half of which are in fact above 99% for the vast majority of Brucella strains. Only one case of B. melitensis biovar 1 has been incorrectly classified. The rest of the microorganisms studied (Staphylococcus aureus, Strteptococcus pyogenes, Enterococcus faecalis, Corynebacterium pseudodiphtheriticum, Clostridium perfringens, Escherichia coli, Acinetobacter calcoaceticus and Pseudomonas aeruginosa) have been classified correctly in all cases to a likelihood of over 80%. In the graphic representation of the analysis, a grouping of these can be seen in clusters, which include the different species. One of these comprises B. melitensis, another Brucella abortus, and another wider one is made up of Brucella suis. The Brucella canis, Brucella ovis and Brucella neotomae strains appear separate from the previously described groups.

Thermolytical techniques to characterize fungal polysaccharides and bacterial lipopolysaccharides.

The present work constitutes an entirely novel contribution in the scope of microbiology and especially in taxonomy, introducing thermolysis curves as a rapid method of characterization of fungal polysaccharides and bacterial lipopolysaccharides. The thermal analysis techniques applied were thermogravimetry and derivative thermogravimetry (TG-DTG), differential thermal analysis (DTA), and differential scanning calorimetry (DSC). Each thermogram of a sample is represented by one or a few temperatures and, in DSC, by complementary enthalpy data. The temperatures of the thermograms from structurally unknown polysaccharides are compared with those used as references, and thus, information on their composition, linkage types, and anomeric configuration can be deduced. The situation is more complicated for bacterial lipopolysaccharides, but in whatever mode, a structural estimation is always possible. In the course of the development and validation of the thermal method, structural findings on relative stabilities of linkage types (valuable in carbohydrate research) have been recognized and are therefore also described in this work.

[Heart pathology of the extracardiac origin. X. Heart diseases of viral etiology]. / Patología del corazón de origen extracardíaco (X). Enfermedades cardíacas de etiología vírica.

Inflammatory processes affecting the heart frequently involve both the myocardium (myocarditis) and the pericardium (pericarditis). The syndromes of myocarditis and pericarditis are sufficiently distinct in clinical presentation and pathophysiology to warrant separate consideration. Viruses are the most important infectious cause of myocarditis in Western Europe. Enteroviruses and especially group B Coxsackie have been the major agents implicated. Patients may be asymptomatic or may have a rapidly progressive fatal disease. The gold standard for the diagnosis is endomyocardial biopsy. The application of "in situ" hybridization techniques and methods that detect or amplify viral nucleic acids may prove useful. Treatment of myocarditis should be directed at the specific etiology agent involved whenever possible. Because of the difficulties encountered in establishing a specific etiologic diagnosis, most cases of acute self-limited pericarditis are classified as idiopathic. Many of these are likely to be caused by viruses. As with myocarditis, most diagnose have been based upon the isolation of the virus from other body sites and/or demonstration of at least a fourfold rise in antibody titer after the acute illness. Among the challenges for the future will be the application of new techniques to expand our understanding at the molecular level of how viruses interact with target cell to alter function. Improved understanding of these aspects should lead to new approaches to the diagnosis, prevention and therapy of viral diseases.

[Genotypes of hepatitis C virus: their relationship with risk factors, the severity of liver disease, and the serologic response]. / Genotipos del virus de la hepatitis C: relación con los factores de riesgo, con la gravedad de la enfermedad hepática y con la respuesta serológica.

BACKGROUND: The objective of our study was to ascertain the prevalence of different HCV genotypes between the hepatitis C patients in the health area of Monforte de Lemos, Spain, as well as the possible influence of risk factors on their distribution and their relation with hepatic disease and with the serologic response. PATIENTS AND METHODS: We have studied 128 patients with hepatitis C. Of these, 41 were intravenous drug users (IVDU), 19 had received transfusions, 7 were hemodialyzed and in 61 the risk factors were unknown. Antibodies against HCV were detected by second-generation enzyme immunoassay (EIA) and confirmed by immunoblot. RNA-HCV presence was studied by reverse transcription-PCR (RT-PCR), and a reverse hybridization test of the amplifications was used for the genotyping. RESULTS: Hepatitis C genotypes 1b (46.1 [8.6%]), 1a (23.4 [7.3%]) and 3a (13.3 [5.9%]) were the most frequently encountered genotype. Genotype 1a (48.8 [15.3%]) was the most prevalent genotypes in IVDU patients, while 1b was the most frequent in patients of unknown risk factors (62.3 [12.1%]). Alanine-aminotransferase (ALT) was elevated in 66.6 (17.7%) of patients with genotype 1a, in 87.5 (8.6%) of patients with genotype 1b (p = 0.0367) and in 94.1 (11.2%) of patients with genotype 3a (p = 0.0347). Subtype 1b was present in 6 of 7 cases of cirrhosis (85.7%) and in 7 of 12 cases of active chronic hepatitis (58.3%). No significant statistical differences were observed between the genotypes and the specific IgM response against core antigen of HCV, neither we observed differences in the serologic response against C1, C2, NS3 and NS4 peptides. CONCLUSIONS: Hepatitis C genotypes 1a and 3a were the most prevalent genotypes between IVDU patients while genotype 1b was the most frequent between non-IVDU patients. Genotype 1b was associated to severe liver disease. Percentage of positivity or the reactivity against HCV peptides was independent of the genotype encountered in the patient.

[Laboratory diagnosis and serologic course in patients with tularemia]. / Diagnóstico de laboratorio y evolución serológica de pacientes con tularemia.

BACKGROUND: Tularemia was practically unknown in Spain until the end of 1997, when an epidemic outbreak was declared. This paper presents the data on microbiological diagnosis of 55 patients who suffered from tularemia. PATIENTS AND METHODS: Thirty-two samples from 19 patients and 151 serum samples from 55 patients were obtained for culture. Serologic diagnosis was performed by tube sero-agglutination and microagglutination. Three types of tests were performed on all sera: Wright sero-agglutination (WSA), Coombs test against Brucella spp. and sero-agglutination against Yersinia enterocolitica O:3, Yersinia enterocolitica O:3, and Proteus OX 19. RESULTS: F. tularensis was found in two samples (6.25%) of the 32 received. Titers > or = 1/160 were obtained in 78.2% and 74.5% of the initial sera by tube sero-agglutination and microagglutination, respectively. Correlation between the two tests was 0.80 (p < 0.001). Prozone phenomenon was observed in 59.9% of the sera, while crossed reactivity to Brucella spp. and Proteus spp. was found in 9.3% and 22.8%, respectively. No crossed reactivity was observed with Yersinia spp. CONCLUSIONS: Culture of F. tularensis has low sensitivity. The correlation obtained between tube sero-agglutination and microagglutination is good. Both techniques are useful in routine diagnosis of tularemia, although microagglutination has some advantages over tube agglutination.

[Paratesticular tumor. Liposarcoma of the spermatic cord]. / Tumor paratesticular. Liposarcoma del cordón espermático.

Liposarcoma of the spermatic cord is a rare tumour typically presenting in elderly people. It tends to grow around blood vessels. Most of them have a low level of malignancy and relapses tend to be localized. Metastasis, when present, occur through the haematological route, lymph spread being very unusual. Pre-operative diagnosis is infrequent and overall prognosis is good. The choice treatment is radical orchidectomy, while long-term follow-up of these patients is mandatory. When local relapses become evident, the choice treatment is extensive local excision, followed by optional adjuvant radiotherapy. Chemotherapy has not proven to be effective. This paper reviews the current literature and contributes one case of mixed liposarcoma of the spermatic cord.

La consulta médica, su tiempo y duración / Medical consultation, time and duration

Resumen: Este es un ensayo en el cual se hace la reflexión sobre el tiempo y la duración de la consulta médica, vistos como procesos sociales que están determinados por macro estructuras, siguiendo la lógica productiva y las demandas del tiempo moderno. La duración de la consulta médica es heterogénea a nivel mundial. Por el contrario, si hay algo en común es la percepción tanto de los profesionales como de los pacientes que el tiempo de interacción es breve, lo cual permea en la relación médico-paciente, perpetuando un ciclo de insatisfacción-tensión-ansiedad en ambos actores. Bajo la premisa de una sociología del tiempo y apelando a los principios éticos de la medicina, proponemos que la estimación en la duración de una consulta considere este recurso como indispensable para una adecuada interacción, teniendo presente las opiniones tanto de los pacientes como de los profesionales en cuanto a sus necesidades de dignidad para la atención y para la prestación de un servicio profesional, ya que ambos tienen derechos y obligaciones a respetarse. Además, las instituciones deberán garantizarlas a fin de preservar una adecuada relación médico-paciente-institución. La organización en los horarios de las jornadas laborales no basta. Es necesario realizar las asignaciones de consulta y tareas correlativas con los tiempos de dedicación necesarios con el objeto de humanizar los procesos, considerando las lógicas sociales y económicas sin ignorar la otredad y la alteridad de los sujetos involucrados.

Abstract: This essay is a reflection of the time and duration of the medical consultation, seen as a social process that is determined by macro structures following the productive logic and the demands of modern time. The length of the medical discussion is heterogeneous worldwide; in contrast, what is standard is the perception of the professionals and the patients that the time for interaction is short. Such a perception pervades the doctor-patient relationship, perpetuating a cycle of dissatisfaction-tension-anxiety in these actors. Under the premise of the sociology of time and appealing to the ethical principles of medicine, we propose that the estimation in the length of a medical consultation must be considered. Time is indispensable for an adequate interaction to account for the needs of patients and professionals in a dignified manner since both have rights and obligations to be respected.