Molecular characterization of hepatitis B virus X gene in chronic hepatitis B patients

Background: HBV-X protein is associated with the pathogenesis of HBV related diseases, specially in hepatocellular carcinomas of chronic patients. Genetic variability of the X gene includes genotypic specific variations and mutations emerging during chronic infection. Its coding sequence overlaps important regions for virus replication, including the basal core promoter. Differences in the X gene may have implications in biological functions of the protein and thus, affect the evolution of the disease. There are controversial results about the consequences of mutations in this region and their relationship with pathogenesis. The purpose of this work was to describe the diversity of HBV-X gene in chronic hepatitis patients infected with different genotypes, according to liver disease. Methods. HBV-X gene was sequenced from chronic hepatitis B patient samples, analyzed by phylogeny and genotyped. Nucleotide and aminoacid diversity was determined calculating intragenetic distances. Mutations at 127, 130 and 131 aminoacids were considered in relation to liver disease. Results: The most prevalent genotype detected in this cohort was F (F1 and F4), followed by D and A. Most of the samples corresponding to genotypes A and F1 were HBeAg(+) and for genotypes D and F4, HBeAg(-) samples were represented in a higher percentage. Intragenetic distance values were higher in HBeAg(-) than in positive samples for all genotypes, and lower in overlapped regions, compared to single codification ones. Nucleotide and aminoacid diversities were higher in HBeAg(-), than in HBeAg(+) samples. Conclusions: Independently of the infecting genotypes, mutations at any of 127, 130 and/or 131 aminoacid positions and HBeAg(-) status were associated with mild liver disease in this cohort.Fil: Barbini, Luciana Fernanda. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Tadey, Luciana. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Fernandez, Silvina. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; ArgentinaFil: Bouzas, Belén. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; ArgentinaFil: Campos, Rodolfo Hector. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

A holistic methodology for the non-destructive experimental characterization and reliability-based structural assessment of historical steel bridges

Financiado para publicación en acceso aberto: Universidade de Vigo/CISUGNowadays, several historical steel structures present damage and an advanced deterioration state induced by human or natural actions, causing fluctuations in geometrical, physical, and mechanical properties that dramatically affect their mechanical behavior. Due to the economic, cultural, and heritage value, these constructions must be comprehensively assessed to verify their current condition state. This work presents a holistic methodology aimed at the non-destructive experimental characterization and reliability-based structural assessment of historical steel bridges. It comprehends from the experimental data acquisition to the finite element model updating and the probabilistic-based structural assessment to obtain the reliability indexes of serviceability and ultimate limit states. Several sources of information are considered in the evaluation process, thus, results are more realistic and accurate and can be used for optimal decision-making related to maintenance and retrofitting actions. The feasibility of the methodology has been tested on O Barqueiro Bridge, an aging riveted bridge located in Galicia, Spain. The study first involved a comprehensive experimental campaign to characterize the bridge effectively at multiple levels: geometry, material, and structural system by the synergetic combination of different tools and methods: in-depth visual inspection, terrestrial laser scanner survey, ultrasonic testing, and ambient vibration test. Subsequently, a detailed FE model was developed and calibrated with an average relative error in frequencies of 2.04% and an average MAC value of 0.94. Finally, the reliability-based structural assessment was performed, yielding reliability indexes of 1.80 and 1.99 for the serviceability and ultimate limit states, respectively. Thus, the bridge could not withstand traffic loads with satisfactory structural performance in its current condition.Ministerio de Ciencia, Innovación y Universidades | Ref. RTI2018-095893-B-C21European Regional Development Fund | Ref. EAPA_826/201

Molecular and biological characterization of hepatitis B virus subgenotype F1b clusters: Unraveling its role in hepatocarcinogenesis

Hepatitis B virus (HBV) subgenotype F1b infection has been associated with the early occurrence of hepatocellular carcinoma in chronically infected patients from Alaska and Peru. In Argentina, however, despite the high prevalence of subgenotype F1b infection, this relationship has not been described. To unravel the observed differences in the progression of the infection, an in-depth molecular and biological characterization of the subgenotype F1b was performed. Phylogenetic analysis of subgenotype F1b full-length genomes revealed the existence of two highly supported clusters. One of the clusters, designated as gtF1b Basal included sequences mostly from Alaska, Peru and Chile, while the other, called gtF1b Cosmopolitan, contained samples mainly from Argentina and Chile. The clusters were characterized by a differential signature pattern of eight nucleotides distributed throughout the genome. In vitro characterization of representative clones from each cluster revealed major differences in viral RNA levels, virion secretion, antigen expression levels, as well as in the localization of the antigens. Interestingly, a differential regulation in the expression of genes associated with tumorigenesis was also identified. In conclusion, this study provides new insights into the molecular and biological characteristics of the subgenotype F1b clusters and contributes to unravel the different clinical outcomes of subgenotype F1b chronic infections.Fil: Elizalde, Maria Mercedes. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Mojsiejczuk, Laura Noelia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Virología; ArgentinaFil: Speroni, Micaela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Bouzas, Belén. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; ArgentinaFil: Tadey, Luciana. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Mammana, Lilia. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; ArgentinaFil: Campos, Rodolfo Hector. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Flichman, Diego Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentin

Model updating of in‐service bridges using multidisciplinary research ‐ case studies in Spain

This paper presents several experiences focused to create and update accurate numerical models of ageing bridges in Spain. The experimental campaigns included integration of various NDT technologies such as laser scanning, ultrasounds, etc., combined with vibration‐based methods such as Operational Modal Analysis. From these multi‐source data it was possible to create an accurate numerical model of each structure, which was lately subjected to a calibration using the actual dynamic response of the structure. Thus, the updated structural model presents the same behaviour as the real construction, offering a powerful tool to more accurately predict the safety level of the structure. On the other hand, structural assessments based on reliability analysis has been proved to improve the quality and accuracy of safety analysis due to the consideration of the possible deviations presented in the parameters of a structure. These works were compiled as case‐studies in Spain within IM‐SAFE project.Agencia Estatal de Investigación | Ref. PRE2019-08733

Quantitative HBsAg an unreliable marker for diagnosis and disease progression in genotype F chronic HBeAg-negative infections

Quantitative hepatitis B surface antigen (qHBsAg) has been proposed as a biomarker to distinguish HBeAg-negative chronic infections (ENI) from HBeAg-negative chronic hepatitis (ENH), identify patients prone to achieving sustained HBsAg loss, and predict the risk of liver disease progression. There is evidence that qHBsAg varies among genotypes, however there is a paucity of data on genotype F. The aim of this study was to investigate the performance of qHBsAg in the diagnosis and evolution of genotype F chronic HBeAg-negative infections. HBV-DNA and HBsAg levels from 153 patients with ENI were correlated with the genotype. Liver disease progression was assessed by abdominal ultrasound and a transient elastography. The qHBsAg levels were significantly different among genotypes (p 3.0 log10 IU/ml, no cases of advanced liver disease were observed at the end of follow-up. This study provides new insights into the impact of HBV genotypes, in particular GTF, on serum HBsAg levels, emphasizing the need to implement a genotype-specific cut-off to achieve diagnostic certainty in the identification of ENI and the risk of liver disease progression. Regardless of HBV genotype, qHBsAg has been shown to be a powerful and reliable biomarker for predicting HBsAg loss.Fil: Fainboim, Hugo. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; ArgentinaFil: Di Benedetto, Nicolas. Hospital Arrecifes; ArgentinaFil: Paz, Silvia. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; ArgentinaFil: Mendizabal, Manuel. Universidad Austral; ArgentinaFil: Campuzano, Soledad. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; ArgentinaFil: Elizalde, Maria Mercedes. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Tadey, Luciana. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Deluchi, Gabriel. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; ArgentinaFil: Bouzas, María Belén. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; ArgentinaFil: Mammana, Lilia. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; ArgentinaFil: Flichman, Diego Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentin

Detection of HIV-1 dual infections in highly exposed treated patients

<p>Abstract</p> <p>Background</p> <p>Genetic characterization of HIV-1 in Argentina has shown that BF recombinants predominate among heterosexuals and injecting drug users, while in men who have sex with men the most prevalent form is subtype B.</p> <p>Objectives</p> <p>The aim of this work was to investigate the presence of HIV dual infections in HIV-infected individuals with high probability of reinfection</p> <p>Study design</p> <p>Blood samples were collected from 23 HIV positive patients with the risk of reinfection from Buenos Aires. A fragment of the HIV gene <it>pol </it>was amplified and phylogenetic analyses were performed. Antiretroviral drug resistance patterns of all the sequences were analyzed.</p> <p>Results</p> <p>Five dual infections were detected with four patients coinfected with subtype B and BF recombinants and one patient was coinfected with two BF recombinants presenting different recombination patterns. Prolonged infection with a stable clinical condition was observed in the five individuals. Resistance mutation patterns were different between the predominant and the minority strains.</p> <p>Conclusions</p> <p>Our results show that HIV dual infection can occur with closely related subtypes, and even with different variants of the same recombinant form in certain populations. Clinical observations showed neither aggressive disease progression nor impact on the resistance patterns in the dually-infected patients.</p

Hematoma Asfixiante Tardío.

En la práctica anestésica diaria, con el objetivo de monitorizar la presión venosa central para control hemodinámico (precarga, introducir un swan ganz para vigilar la presión arterial pulmonar...) o infundir drogas vasopresoras, se canaliza una vía venosa central, yugular o subclavia. Aunque la tasa complicaciones es baja, esta técnica no está exenta de riesgos: hemotórax, pseudoaneurisma, fístula arterio-venosa, lesión vascular venosa, hematoma, punción arterial, entre otras. La tasa de punción arterial durante el proceso de canalización de una vía central varía del 3,7 al 8% según las distintas series y la aparición de un hematoma está entorno al 0,8%. Los hematomas asfixiantes secundarios a la punción arterial durante la canalización de una vía central son extremadamente raros, y desgraciadamente de diagnóstico tardío. Normalmente ocurren tras una punción arterial, la mayoría de las veces de la arteria carótida, seguida de la dilatación y/o canalización de la misma (rara vez se dan tras punción en arteria subclavia y/o punción única arterial sin dilatación y/o canalización) y mayoritariamente en pacientes con factores de riesgo tales como: alteraciones de la coagulación o tratamiento antiagregante y/o anticoagulante

Immunogenicity induced by the use of alternative vaccine platforms to deal with vaccine shortages in a low- to middle-income country: Results of two randomized clinical trials

Background: Shortages of component two of Sputnik V vaccine (rAd5) are delaying the possibility of achieving full immunisation. The immunogenic response associated with the use of alternative schemes to complete the scheme was not explored. Methods: We did two non-inferiority randomized clinical trials with outcomes measures blinded to investigators on adults aged 21–65 years, vaccinated with a single dose of rAd26 ≥ 30 days before screening and no history of SARS-CoV-2. Participants were assigned (1:1:1:1:1) to receive either rAd5; ChAdOx1; rAd26; mRNA-1273 or BBIBP-CorV. The primary endpoint was the geometric mean ratio (GMR) of SARS-CoV-2 anti-spike IgG concentration at 28 days after the second dose, when comparing rAd26/rAd5 with rAd26/ChAdOx1, rAd26/rAd26, rAd26/mRNAmRNA-1273 and rAd26/BBIBP-CorV. Serum neutralizing capacity was evaluated using wild type SARS-CoV-2 reference strain 2019 B.1. The safety outcome was 28-day rate of serious adverse. The primary analysis included all participants who received ≥ 1 dose. The studies were registered with NCT04962906 and NCT05027672. Both trials were conducted in Buenos Aires, Argentina. Findings: Between July 6 and August 3, 2021, 540 individuals (age 56·7 [SD 7·3]; 243 (45%) women) were randomly assigned to received rAd5 (n=150); ChAdOx1 (n=150); rAd26 (N=87); mRNAmRNA-1273 (n=87) or BBIBP-CorV (n=65). 524 participants completed the study. As compared with rAd26/rAd5 (1·00), the GMR (95%CI) at day 28 was 0·65 (0·51–0·84) among those who received ChAdOx1; 0·47 (0·34–0·66) in rAd5; 3·53 (2·68–4·65) in mRNA-1273 and 0·23 (0·16–0·33) in BBIBP-CorV. The geometric mean (IU/ml) from baseline to day 28 within each group increased significantly with ChAdOx1 (4·08 (3·07–5·43)); rAd26 (2·69 (1·76–4·11)); mRNA-1273 (21·98 (15·45–31·08)) but not in BBIBP-CorV (1·22 (0·80–1·87)). Interpretation: Except for mRNA-1273 which proved superior, in all other alternatives non-inferiority was rejected. Antibody concentration increased in all non-replicating viral vector and RNA platforms. Funding: The trials were supported (including funding, material support in the form of vaccines and testing supplies) by the Buenos Aires City Government.Fil: Macchia, Alejandro. No especifíca;Fil: Ferrante, Daniela. No especifíca;Fil: Bouzas, María Belén. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; ArgentinaFil: Angeleri, Patricia. No especifíca;Fil: Biscayart, Cristián. No especifíca;Fil: Geffner, Jorge Raúl. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Mammana, Lilia. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; ArgentinaFil: Zapiola, Inés. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; ArgentinaFil: López, Eduardo Luis. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Gentile, Angela. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Varese, Augusto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Mazzitelli, Ignacio Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Di Diego García, Facundo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Sharff, Deborah. No especifíca;Fil: Lucconi, Verónica. No especifíca;Fil: Sujansky, Paula. No especifíca;Fil: Mariani, Javier. No especifíca;Fil: González Bernaldo de Quirós, Fernán. No especifíca

Comparative validation of three contemporary bleeding risk scores in acute coronary syndromes

Background: Hemorrhagic complications are strongly linked with subsequent adverse outcomes in acute coronary syndrome (ACS) patients. Various risk scores (RS) are available to estimate the bleeding risk in these patients. Aims: To compare the predictive accuracy of the three contemporary bleeding RS in ACS. Methods: We studied 4500 consecutive patients with ACS. For each patient, the ACTION, CRUSADE, and Mehran et al bleeding RS were calculated. We assessed their performance either for the prediction of their own major bleeding events or to predict the TIMI serious (major and minor) bleeding episodes in the overall population, in patients with non-ST elevation ACS (NSTEACS) and in those with ST-elevation myocardial infarction (STEMI) patients. Calibration (Hosmer-Lemeshow test) and discrimination (c-statistic) for the three RS were computed and compared. We used the concept of net reclassification improvement (NRI) to compare the incremental prognostic value of using a particular RS over the remaining scores in predicting the TIMI serious bleeding. Results: The best predictive accuracy was obtained by the CRUSADE score either for the prediction of its own major bleeding events (c-statistic=0.80, 0.791, and 0.81 for the entire sample, for STEMI, and for NSTEACS patients, respectively) or to predict the TIMI serious bleed occurrence (c-statistic=0.741, 0.738,and 0.745 for the whole population, for STEMI and NSTEACS patients, respectively). The lowest bleeding rates observed in patients classified as low risk corresponded to the CRUSADE RS. All scores performed modestly in patients who did not undergo coronariography (all c-statistic <0.70). The CRUSADE score was significantly superior to the ACTION model in predicting the TIMI serious bleeding occurrence in terms of NRI overall and by ACS subgroups (p<0.05). Overall, the CRUSADE RS exhibited better calibration for predicting the TIMI serious bleeding compared to the ACTION and Mehran et al scores (Hosmer-Lemeshow p-values of 0.26, 0.13, and 0.07, respectively). Conclusion: The CRUSADE score represents, among the more contemporary bleeding RS, the most accurate and reliable quantitative clinical tool in STEACS and STEMI patients. We encourage the utilization of the CRUSADE index for bleeding risk stratification purposes in daily clinical practice and in ACS outcome studies. The performance of the three more contemporary bleeding RS is modest in those patients who received conservative management