42 results on '"Trinks, J."'
Search Results
2. Hepatitis C virus pharmacogenomics in Latin American populations: implications in the era of direct-acting antivirals
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Trinks J, Caputo M, Hulaniuk ML, Corach D, and Flichman D
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Hepatitis C virus ,pharmacogenomics ,PEG-IFN/RBV ,DAAs ,Latin America ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Julieta Trinks,1,2 Mariela Caputo,2,3 María L Hulaniuk,1 Daniel Corach,2,3 Diego Flichman2,4 1Basic Science and Experimental Medicine Institute (ICBME), University Institute of the Italian Hospital of Buenos Aires, 2Scientific and Technological National Research Council (CONICET), 3Servicio de Huellas Digitales Genéticas, Facultad de Farmacia y Bioquímica, 4Cátedra de Virología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina Abstract: In recent years, great progress has been made in the field of new therapeutic options for hepatitis C virus (HCV) infection. The new direct-acting antiviral agents (DAAs) represent a great hope for millions of chronically infected individuals because their use may lead to excellent cure rates with fewer side effects. In Latin America, the high prevalence of HCV genotype 1 infection and the significant association of Native American ancestry with risk predictive single-nucleotide polymorphisms (SNPs) in IFNL4 and ITPA genes highlight the need to implement new treatment regimens in these populations. However, the universal accessibility to DAAs is still not a reality in the region as their high cost is one of the major, although not the only, limiting factors for their broad implementation. Therefore, under these circumstances, could the assessment of host genetic markers be a useful tool to prioritize DAA treatment until global access to these new drugs can be achieved? This review will summarize the scientific evidences and the potential implications of HCV pharmacogenomics in this rapidly evolving era of anti-HCV drug development. Keywords: hepatitis C virus, pharmacogenomics, PEG-IFN/RBV, DAAs, Latin America
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- 2017
3. Gesellschaftsrechtliche Wahlverwandtschaften: französische SAS und europäische SES
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Trinks, J.
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- 2023
4. Clinical utility of pharmacogenomics in the management of hepatitis C
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Trinks J, Hulaniuk ML, Redal MA, and Flichman D
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Therapeutics. Pharmacology ,RM1-950 - Abstract
Julieta Trinks,1,2 María Laura Hulaniuk,1 María Ana Redal,1,3 Diego Flichman2,4 1Instituto de Ciencias Básicas y Medicina Experimental, Hospital Italiano de Buenos Aires, 2National Scientific and Technical Research Council, 3Instituto Universitario del Hospital Italiano de Buenos Aires, 4Cátedra de Virología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina Abstract: Hepatitis C virus (HCV) was identified for the first time more than 20 years ago. Since then, several studies have highlighted the complicated aspects of this viral infection in relation to its worldwide prevalence, its clinical presentation, and its therapeutic response. Recently, two landmark scientific breakthroughs have moved us closer to the successful eradication of chronic HCV infection. First, response rates in treatment-naïve patients and in prior non-responders to pegylated-interferon-α and ribavirin therapy are increasing as a direct consequence of the development of direct-acting antiviral drugs. Secondly, the discovery of single-nucleotide polymorphisms near the interleukin 28B gene significantly related to spontaneous and treatment-induced HCV clearance represents a milestone in the HCV therapeutic landscape. The implementation of this pharmacogenomics finding as a routine test for HCV-infected patients has enhanced our understanding of viral pathogenesis, has encouraged the design of ground-breaking antiviral treatment regimens, and has become useful for pretreatment decision making. Nowadays, interleukin 28B genotyping is considered to be a key diagnostic tool for the management of HCV-infected patients and will maintain its significance for new combination treatment schemes using direct-acting antiviral agents and even in interferon-free regimens. Such pharmacogenomics insights represent a challenge to clinicians, researchers, and health administrators to transform this information into knowledge with the aim of elaborating safer and more effective therapeutic strategies specifically designed for each patient. In conclusion, the individualization of treatment regimens for patients with hepatitis C, that may lead to a universal cure in future years, is becoming a reality due to recent developments in biomarker and genomic medicine. In light of these advances, we review the scientific evidence and clinical implications of recent findings related to host genetic factors in the management of HCV infection. Keywords: hepatitis C virus, pharmacogenomics, interleukin 28B, inosine triphosphatase
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- 2014
5. Distribution of genetic polymorphisms associated with hepatitis C virus (HCV) antiviral response in a multiethnic and admixed population
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Trinks, J, Hulaniuk, M L, Caputo, M, Pratx, L Burgos, Ré, V, Fortuny, L, Pontoriero, A, Frías, A, Torres, O, Nuñez, F, Gadano, A, Corach, D, and Flichman, D
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- 2014
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6. Schadensersatz wegen pflichtwidriger Gewinnthesaurierung im GmbH-Recht
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Trinks, J.
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- 2021
7. A simple and rapid approach for human herpesvirus type 8 subtype characterization using single base extension
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Hulaniuk, M.L., primary, Corach, D., additional, Trinks, J., additional, and Caputo, M., additional
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- 2021
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8. OC-0220: Treatment planning without user interaction: Automatic plan approval of prostate Auto-Plans
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Kiers, K., primary, Van der Bijl, E., additional, Trinks, J., additional, Hogaarts, A., additional, Van der Bel, R., additional, Wortel, G., additional, Damen, E., additional, and Tomas, J., additional
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- 2020
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9. Genotypes B and C hepatocellular carcinoma–associated hepatitis B virus pre-S mutants: their detection among F1b and A2 – but not F4 – isolates from Argentina
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Trinks, J., Frías, S., Frider, B., Alessio, A., Pozzati, M., Daleoso, G., León, L., Batalla, V. M., Díaz, A., Ameigeiras, B., and Oubiña, J. R.
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- 2012
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10. Two simultaneous hepatitis B virus epidemics among injecting drug users and men who have sex with men in Buenos Aires, Argentina: characterization of the first D/A recombinant from the American continent
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Trinks, J., Cuestas, M. L., Tanaka, Y., Mathet, V. L., Minassian, M. L., Rivero, C. W., Benetucci, J. A., Gímenez, E. D., Segura, M., Bobillo, M. C., Corach, D., Ghiringhelli, P. D., Sánchez, D. O., Ávila, M. M., Peralta, L. A. M., Kurbanov, F., Weissenbacher, M. C., Simmonds, P., Mizokami, M., and Oubiña, J. R.
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- 2008
11. EP-1985 Clinical feasibility of CBCT-based online plan adaptation for multiple lesion brain SRS
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Wortel, G., primary, Stankovic, U., additional, Trinks, J., additional, Sotiropoulos, G., additional, Van Kranen, S., additional, Van de Water, S., additional, Van de Schoot, S., additional, Dewit, L., additional, Damen, E., additional, Janssen, T., additional, Remeijer, P., additional, and Sonke, J., additional
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- 2019
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12. EP-2123: Clinical evaluation of an auto-segmentation toolbox for breast CTV
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Simões, R., primary, Rozendaal, R., additional, Trinks, J., additional, Kalisvaart, R., additional, Van der Heide, U., additional, and Remeijer, P., additional
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- 2018
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13. SP-0645: Automated treatment planning at NKI: benefits and challenges
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Damen, E., primary, Harmsen, R., additional, Wortel, G., additional, Olszewska, A., additional, Van der Veen, G., additional, Retel, G., additional, Pronk, P., additional, Eekhout, D., additional, Duijn, A., additional, Lamers, E., additional, Tijhuis, A., additional, Janssen, T., additional, Wiersma, T., additional, De Graaf, R., additional, and Trinks, J., additional
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- 2018
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14. OC-0252: Acceptance rates of automatically generated treatment plans for breast cancer
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Van der Veen, G., primary, Duijn, A., additional, Trinks, J., additional, Scholten, A., additional, Harmsen, R., additional, Wortel, G., additional, De Graaf, R., additional, Den Boer, D., additional, and Damen, E., additional
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- 2017
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15. PO-0818: Improving plan quality and efficiency by automated rectum VMAT treatment planning
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Wortel, G., primary, Trinks, J., additional, Eekhout, D., additional, De Ruiter, P., additional, De Graaf, R., additional, Dewit, L., additional, and Damen, E., additional
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- 2017
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16. EP-1628: Single-click automatic radiotherapy treatment planning for breast, prostate and vertebrae
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De Graaf, R., primary, Trinks, J., additional, Duijn, A., additional, Knegjens, J., additional, Eekhout, D., additional, Harmsen, R., additional, Olszewska, A., additional, Retèl, G., additional, Wortel, G., additional, Sanden, S.V.d., additional, Buiter, M., additional, Vliet-Vroegindeweij, C. Van, additional, and Damen, E., additional
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- 2016
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17. EP-1639: Single-click generation of whole breast IMRT treatment plans
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Wortel, G., primary, Harmsen, R., additional, Trinks, J., additional, Duijn, A., additional, De Graaf, R., additional, Scholten, A., additional, Van Vliet-Vroegindeweij, C., additional, and Damen, E., additional
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- 2016
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18. CSI-EPT: A novel contrast source approach to MRI based electric properties tomography and patient-specific SAR
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Balidemaj, Edmond, Trinks, J., Berg van den, C. A. T., Nederveen, A., van Lier, A. L., Stalpers, L. J. A., Crezee, H., Remis, R. F., Anonymous, A., Radiotherapy, Amsterdam Cardiovascular Sciences, Amsterdam Neuroscience, Radiology and Nuclear Medicine, and Cancer Center Amsterdam
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Electromagnetic field ,Physics ,medicine.diagnostic_test ,Iterative method ,business.industry ,media_common.quotation_subject ,Physics::Medical Physics ,Magnetic resonance imaging ,Dielectric ,Nuclear magnetic resonance ,Optics ,Region of interest ,Electric field ,medicine ,Contrast (vision) ,Tomography ,business ,media_common - Abstract
In this paper, we present a novel method (Contrast Source Inversion - Electric Properties Tomography or CSI-EPT) to dielectric imaging of biological tissue using so-called B1+ data measurable by Magnetic Resonance Imaging (MRI) systems. Integral representations for the electromagnetic field quantities are taken as a starting point and we follow an iterative contrast source inversion approach to retrieve the dielectric tissue parameters from measured field data. Numerical results illustrate the performance of the method and show that reliable results are produced near tissue boundaries as opposed to the currently used methods. Fine structures can be resolved as well and since CSI-EPT reconstructs the electric field strength inside a scanning region of interest, it is also a promising candidate to determine the patient-specific SAR deposition during an MRI scan.
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- 2013
19. P28: In vitro replication competence of a hepatitis B genotype D/A recombinant virus: dissimilar biological behaviour regarding its parental genotypes
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Trinks, J, primary, Sugiyama, M, additional, Tanaka, Y, additional, Kurbanov, F, additional, Benetucci, J, additional, Gimenez, E, additional, Weissenbacher, M, additional, Mizokami, M, additional, and Oubina, J, additional
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- 2013
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20. P9: Distribution of genetic polymorphisms associated to hepatitis C virus (HCV) antiviral response in a multiethnic and admixed population
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Trinks, J, primary, Caputo, M, additional, Hulaniuk, M, additional, Burgos Pratx, L, additional, Re, V, additional, Fortuny, L, additional, Frias, A, additional, Torres, O, additional, Nunez, F, additional, Gadano, A, additional, Corach, D, additional, and Flichman, D, additional
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- 2013
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21. GB virus C quasispecies detected in plasma and lymphocyte subsets in a natural human infection
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Ruiz, V., primary, Giordano, M., additional, Rivero, C. W., additional, Minassian, M. L., additional, Cuestas, M. L., additional, Trinks, J., additional, Mathet, V. L., additional, and Oubina, J. R., additional
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- 2010
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22. Dichtung und Anschauung. Narrative Identität und phänomenologische Beschreibung
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Cristin, Renato, Trinks J. (Hg.), and Cristin, Renato
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narrazione ,identità ,descrizione fenomenologica ,Husserl - Published
- 2002
23. Omics-based biomarkers as useful tools in metabolic dysfunction-associated steatotic liver disease clinical practice: How far are we?
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Trinks J, Mascardi MF, Gadano A, and Marciano S
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- Humans, Proteomics methods, Genomics methods, Non-alcoholic Fatty Liver Disease diagnosis, Non-alcoholic Fatty Liver Disease metabolism, Risk Assessment methods, Liver pathology, Liver metabolism, Liver Cirrhosis diagnosis, Liver Cirrhosis blood, Liver Cirrhosis pathology, Biomarkers analysis, Biomarkers metabolism, Metabolomics methods
- Abstract
Unmet needs exist in metabolic dysfunction-associated steatotic liver disease (MASLD) risk stratification. Our ability to identify patients with MASLD with advanced fibrosis and at higher risk for adverse outcomes is still limited. Incorporating novel biomarkers could represent a meaningful improvement to current risk predictors. With this aim, omics technologies have revolutionized the process of MASLD biomarker discovery over the past decades. While the research in this field is thriving, much of the publication has been haphazard, often using single-omics data and specimen sets of convenience, with many identified candidate biomarkers but lacking clinical validation and utility. If we incorporate these biomarkers to direct patients' management, it should be considered that the roadmap for translating a newly discovered omics-based signature to an actual, analytically valid test useful in MASLD clinical practice is rigorous and, therefore, not easily accomplished. This article presents an overview of this area's current state, the conceivable opportunities and challenges of omics-based laboratory diagnostics, and a roadmap for improving MASLD biomarker research., Competing Interests: Conflict-of-interest statement: Authors declare no conflict of interests for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)
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- 2024
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24. Integrated analysis of the transcriptome and its interaction with the metabolome in metabolic associated fatty liver disease: Gut microbiome signatures, correlation networks, and effect of PNPLA3 genotype.
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Mascardi MF, Mazzini FN, Suárez B, Ruda VM, Marciano S, Casciato P, Narvaez A, Haddad L, Anders M, Orozco F, Tamaroff AJ, Cook F, Gounarides J, Gutt S, Gadano A, García CM, Marro ML, Penas Steinhardt A, and Trinks J
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- Humans, Genotype, Metabolome, Transcriptome genetics, Gastrointestinal Microbiome genetics, Acyltransferases genetics, Phospholipases A2, Calcium-Independent genetics, Non-alcoholic Fatty Liver Disease genetics, Non-alcoholic Fatty Liver Disease microbiology
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Interactions between communities of the gut microbiome and with the host could affect the onset and progression of metabolic associated fatty liver disease (MAFLD), and can be useful as new diagnostic and prognostic biomarkers. In this study, we performed a multi-omics approach to unravel gut microbiome signatures from 32 biopsy-proven patients (10 simple steatosis -SS- and 22 steatohepatitis -SH-) and 19 healthy volunteers (HV). Human and microbial transcripts were differentially identified between groups (MAFLD vs. HV/SH vs. SS), and analyzed for weighted correlation networks together with previously detected metabolites from the same set of samples. We observed that expression of Desulfobacteraceae bacterium, methanogenic archaea, Mushu phage, opportunistic pathogenic fungi Fusarium proliferatum and Candida sorbophila, protozoa Blastocystis spp. and Fonticula alba were upregulated in MAFLD and SH. Desulfobacteraceae bacterium and Mushu phage were hub species in the onset of MAFLD, whereas the activity of Fonticula alba, Faecalibacterium prausnitzii, and Mushu phage act as key regulators of the progression to SH. A combination of clinical, metabolomic, and transcriptomic parameters showed the highest predictive capacity for MAFLD and SH (AUC = 0.96). In conclusion, faecal microbiome markers from several community members contribute to the switch in signatures characteristic of MAFLD and its progression towards SH., (© 2023 Wiley-VCH GmbH.)
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- 2023
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25. Development of a nested real time PCR/high resolution melting assay for human T-cell lymphotropic viruses types 1 and 2 (HTLV-1 and 2) identification.
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Caputo M, Trinks J, Azcurra M, and Corach D
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- Blotting, Western, Human T-lymphotropic virus 2 genetics, Humans, Real-Time Polymerase Chain Reaction, T-Lymphocytes, HTLV-II Infections diagnosis, HTLV-II Infections epidemiology, Human T-lymphotropic virus 1 genetics
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HTLV-1 and HTLV-2 are present in different high-risk populations, such as sexual workers and injecting drug users (IDUs). HTLV-1 is endemic in areas of Middle East, Southern Japan and Latin America, whereas HTLV-2 infection is endemic among some Native Americans and some Central African tribes. The pathogenic consequences and clinical manifestations of these two viruses differ significantly, demanding an adequate identification; therefore, proper diagnosis of HTLV-1 and 2 infection is crucial. To get a final diagnosis of HTLV-1 or 2 infection, it is recommended that positive serologic samples should be confirmed by PCR assays or western blot (WB) analysis. Thus, the aim of this study was to develop and implement a simple reaction for the rapid identification of HTLV-1 and 2. Nested real-time PCR technique followed by high resolution melting was performed based on the tax/rex sequences of HTLV-1 (M2) and HTLV-2 (MoT) cell lines perfectly discriminating between HTLV-1 from HTLV-2, by distinct melting curve profiles. The sensitivity assay of this method revealed that at least 1 viral copy of HTLV-1 or 1·5 viral copy of HTLV-2 could be amplified. Later, this method was validated using 200 blood samples from corpses. In agreement with previous epidemiological, the HTLV-1 and 2 prevalence was 1·5% (CI 95%: 0·31-4·3) and 0·5% (CI 95%: 0·013-2·75), respectively. The strategy proposed herein has some advantages over other PCR-based tests because it not only reduces considerably time and the costs of the total diagnosis but also allows detection and discrimination of HTLV-1 and 2 in the same reaction., (© 2022 The Society for Applied Microbiology.)
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- 2022
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26. A Two-Time Point Analysis of Gut Microbiota in the General Population of Buenos Aires and Its Variation Due to Preventive and Compulsory Social Isolation During the COVID-19 Pandemic.
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Aguilera P, Mascardi MF, Belforte FS, Rosso AD, Quesada S, Llovet I, Iraola G, Trinks J, and Penas-Steinhardt A
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The COVID-19 pandemic poses a great challenge to global public health. The extraordinary daily use of household disinfectants and cleaning products, social distancing and the loss of everyday situations that allow contact between individuals, have a direct impact on the transfer of microorganisms within the population. Together, these changes, in addition to those that occur in eating habits, can affect the composition and diversity of the gut microbiota. A two-time point analysis of the fecal microbiota of 23 Metropolitan Buenos Aires (BA) inhabitants was carried out, to compare pre-pandemic data and its variation during preventive and compulsory social isolation (PCSI) in 2020. To this end, 23 healthy subjects, who were previously studied by our group in 2016, were recruited for a second time during the COVID-19 pandemic, and stool samples were collected from each subject at each time point ( n = 46). The hypervariable region V3-V4 of the 16S rRNA gene was high-throughput sequenced. We found significant differences in the estimated number of observed features ( p < 0.001), Shannon entropy index ( p = 0.026) and in Faith phylogenetic diversity ( p < 0.001) between pre-pandemic group (PPG) vs. pandemic group (PG), being significantly lower in the PG. Although no strong change was observed in the core microbiota between the groups in this study, a significant decrease was observed during PCSI in the phylum Verrucomicrobia, which contributes to intestinal health and glucose homeostasis. Microbial community structure (beta diversity) was also compared between PPG and PG. The differences observed in the microbiota structure by unweighted UniFrac PCoA could be explained by six differential abundant genera that were absent during PCSI. Furthermore, putative functional genes prediction using PICRUSt infers a smaller predicted prevalence of genes in the intestinal tryptophan, glycine-betaine, taurine, benzoate degradation, as well as in the synthesis of vitamin B12 during PCSI. This data supports the hypothesis that the microbiome of the inhabitants of BA changed in the context of isolation during PCSI. Therefore, these results could increase the knowledge necessary to propose strategic nutraceutical, functional food, probiotics or similar interventions that contribute to improving public health in the post-pandemic era., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Aguilera, Mascardi, Belforte, Rosso, Quesada, Llovet, Iraola, Trinks and Penas-Steinhardt.)
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- 2022
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27. Plasma and stool metabolomics to identify microbiota derived-biomarkers of metabolic dysfunction-associated fatty liver disease: effect of PNPLA3 genotype.
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Mazzini FN, Cook F, Gounarides J, Marciano S, Haddad L, Tamaroff AJ, Casciato P, Narvaez A, Mascardi MF, Anders M, Orozco F, Quiróz N, Risk M, Gutt S, Gadano A, Méndez García C, Marro ML, Penas-Steinhardt A, and Trinks J
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- Biomarkers, Genotype, Humans, Lipase genetics, Membrane Proteins genetics, Metabolomics, Microbiota, Non-alcoholic Fatty Liver Disease diagnosis, Non-alcoholic Fatty Liver Disease genetics
- Abstract
Introduction: Non-invasive biomarkers are needed for metabolic dysfunction-associated fatty liver disease (MAFLD), especially for patients at risk of disease progression in high-prevalence areas. The microbiota and its metabolites represent a niche for MAFLD biomarker discovery. However, studies are not reproducible as the microbiota is variable., Objectives: We aimed to identify microbiota-derived metabolomic biomarkers that may contribute to the higher MAFLD prevalence and different disease severity in Latin America, where data is scarce., Methods: We compared the plasma and stool metabolomes, gene patatin-like phospholipase domain-containing 3 (PNPLA3) rs738409 single nucleotide polymorphism (SNP), diet, demographic and clinical data of 33 patients (12 simple steatosis and 21 steatohepatitis) and 19 healthy volunteers (HV). The potential predictive utility of the identified biomarkers for MAFLD diagnosis and progression was evaluated by logistic regression modelling and ROC curves., Results: Twenty-four (22 in plasma and 2 in stool) out of 424 metabolites differed among groups. Plasma triglyceride (TG) levels were higher among MAFLD patients, whereas plasma phosphatidylcholine (PC) and lysoPC levels were lower among HV. The PNPLA3 risk genotype was related to higher plasma levels of eicosenoic acid or fatty acid 20:1 (FA(20:1)). Body mass index and plasma levels of PCaaC24:0, FA(20:1) and TG (16:1_34:1) showed the best AUROC for MAFLD diagnosis, whereas steatosis and steatohepatitis could be discriminated with plasma levels of PCaaC24:0 and PCaeC40:1., Conclusion: This study identified for the first time MAFLD potential non-invasive biomarkers in a Latin American population. The association of PNPLA3 genotype with FA(20:1) suggests a novel metabolic pathway influencing MAFLD pathogenesis.
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- 2021
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28. Genetic diversity and phylogeographic analysis of human herpesvirus type 8 (HHV-8) in two distant regions of Argentina: Association with the genetic ancestry of the population.
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Hulaniuk ML, Mojsiejczuk L, Jauk F, Remondegui C, Mammana L, Bouzas MB, Zapiola I, Ferro MV, Ajalla C, Blejer J, Alter A, Acevedo ME, Rodríguez E, Fernández R, Bartoli S, Volonteri V, Kohan D, Elsner B, Bürgesser MV, Reynaud AL, Sánchez M, González C, García Rivello H, Corach D, Caputo M, and Trinks J
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- Adult, Aged, Argentina epidemiology, Blood Donors statistics & numerical data, Female, Humans, Male, Middle Aged, Phylogeny, Population Surveillance, Genetic Variation, Genetics, Population, Genotype, Herpesvirus 8, Human genetics, Phylogeography statistics & numerical data, Sarcoma, Kaposi epidemiology, Sarcoma, Kaposi genetics
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Background: The genetic diversity of persistent infectious agents, such as HHV-8, correlates closely with the migration of modern humans out of East Africa which makes them useful to trace human migrations. However, there is scarce data about the evolutionary history of HHV-8 particularly in multiethnic Latin American populations., Objectives: The aims of this study were to characterize the genetic diversity and the phylogeography of HHV-8 in two distant geographic regions of Argentina, and to establish potential associations with pathogenic conditions and the genetic ancestry of the population., Study Design: A total of 101 HIV-1 infected subjects, 93 Kaposi's Sarcoma (KS) patients and 411 blood donors were recruited in the metropolitan (MET) and north-western regions of Argentina (NWA). HHV-8 DNA was detected by ORF-26 PCR in whole blood, saliva and FFPE tissues. Then, ORF-26 and ORF-K1 were analyzed for subtype assignment. Mitochondrial DNA and Y chromosome haplogroups, as well as autosomal ancestry markers were evaluated in samples in which subtypes could be assigned. Phylogeographic analysis was performed in the ORF-K1 sequences from this study combined with 388 GenBank sequences., Results: HHV-8 was detected in 50.7%, 59.2% and 8% of samples from HIV-1 infected subjects, KS patients and blood donors, respectively. ORF-K1 phylogenetic analyses showed that subtypes A (A1-A5), B1, C (C1-C3) and F were present in 46.9%, 6.25%, 43.75% and 3.1% of cases, respectively. Analyses of ORF-26 fragment revealed that 81.95% of strains were subtypes A/C followed by J, B2, R, and K. The prevalence of subtype J was more commonly observed among KS patients when compared to the other groups. Among KS patients, subtype A/C was more commonly detected in MET whereas subtype J was the most frequent in NWA. Subtypes A/C was significantly associated with Native American maternal haplogroups (p = 0.004), whereas subtype J was related to non-Native American haplogroups (p < 0.0001). Sub-Saharan Africa, Europe and Latin America were the most probable locations from where HHV-8 was introduced to Argentina., Conclusions: These results give evidence of the geographic circulation of HHV-8 in Argentina, suggest the association of ORF-26 subtype J with KS development and provide new insights about its relationship with ancient and modern human migrations and identify the possible origins of this virus in Argentina., (Copyright © 2020 Elsevier B.V. All rights reserved.)
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- 2020
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29. The genetic variability of hepatitis B virus subgenotype F1b precore/core gene is related to the outcome of the acute infection.
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Trinks J, Marciano S, Esposito I, Franco A, Mascardi MF, Mendizabal M, Livellara B, Arrigo D, Calzetta P, Vujacich C, Giunta D, Gadano A, and Flichman D
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- Acute Disease, Aged, Female, Genotype, Hepatitis B Core Antigens blood, Humans, Male, Middle Aged, Mutation Rate, Polymorphism, Single Nucleotide, Prospective Studies, Quasispecies genetics, Genetic Variation, HLA Antigens genetics, Hepatitis B genetics, Hepatitis B virology, Hepatitis B virus genetics, Point Mutation
- Abstract
Aim: To assess the association of viral and host genetic variability with the outcome of acute infection with hepatitis B virus subgenotype F1b (HBV/F1b)., Methods: The cohort consisted of 26 patients with acute HBV/F1b infection who exhibit different outcomes: spontaneous resolution (n = 10), progression to chronic hepatitis (n = 10) and acute liver failure (n = 6). HLA SNPs (rs3077, rs9277542, rs2856718 and rs7453920) were determined. The S gene and core promoter/precore/core region were direct sequenced, and this latter region was also ultra-deep sequenced. Mean number of mutations, mutation rate, Shannon entropy, positive selection sites and mutational patterns of quasispecies were compared between groups., Results: HLA SNPs were associated with spontaneous resolution or progression to chronic hepatitis, but not with the development of acute liver failure. The mean number of mutations in the S gene was similar among the three groups. Patients with spontaneous resolution had the lowest number of mutations, mutation rates and Shannon entropy values in the precore/core compared to the other two groups. Ten positive selection sites mapped on HLA-restricted epitopes were related to progression to chronic hepatitis and acute liver failure. Mutations T1753C, A1762T, G1764A, C1766T, T1768A G1896A, G2092T and T2107C were associated with acute liver failure and progression to chronic hepatitis., Conclusion: Highly heterogeneous and complex HBV precore/core carrying specific point mutations, combined with the host HLA background, were associated with a worse clinical outcome of acute HBV/F1b infection., (Copyright © 2019 Elsevier B.V. All rights reserved.)
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- 2020
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30. Unexpected high seroprevalence of hepatitis E virus in patients with alcohol-related cirrhosis.
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Fantilli AC, Trinks J, Marciano S, Zárate F, Balderramo DC, Wassaf MGM, Haddad L, Gadano A, Debes JD, Pisano MB, and Ré VE
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- Acute Disease, Adult, Aged, Aged, 80 and over, Case-Control Studies, Cross-Sectional Studies, Female, Humans, Liver Cirrhosis, Alcoholic complications, Male, Middle Aged, Risk Factors, Seroepidemiologic Studies, Young Adult, Hepatitis E complications, Hepatitis E epidemiology, Liver Cirrhosis, Alcoholic virology
- Abstract
Introduction: Little is known about hepatitis E virus (HEV) infection in patients with cirrhosis. The aim of the present study was to describe the frequency of HEV infection and associated risk factors in patients with cirrhosis from Argentina., Materials and Methods: We evaluated HEV seroprevalence (IgG anti-HEV) and acute infections (IgM and RNA) in patients with cirrhosis (n = 140) vs. healthy controls (n = 300). Additionally, we compared the same outcomes in individuals with alcohol-related cirrhosis (n = 43) vs. patients with alcohol use disorder (without cirrhosis, n = 72)., Results: The overall HEV seroprevalence in the cohort of subjects with cirrhosis was 25% (35/140), compared to 4% in the healthy control group [12/300; OR = 8; (95% CI = 4-15.99); p<0.05]. HEV seropositivity was significantly higher in alcohol-related cirrhosis compared to other causes of cirrhosis [39.5% vs. 12.4%; OR = 4.71; (95% CI = 1.9-11.6); p<0.05] and to healthy controls [OR = 15.7; (95% CI = 6.8-36.4); p = 0.0001]. The HEV seroprevalence in alcoholic-related cirrhosis vs. with alcohol use disorder was 39.5% vs. 12.5% [OR = 4.58; (95% CI = 1.81-11.58); p<0.001]., Conclusion: We found a high seroprevalence of HEV in patients with cirrhosis and in individuals with alcohol use disorder. The simultaneous presence of both factors (cirrhosis + alcohol) showed more association to HEV infection. Larger studies with prospective follow up are needed to further clarify this interaction., Competing Interests: The authors have declared that no competing interests exist.
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- 2019
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31. Prevalence and Factors Related to Natural Resistance-Associated Substitutions to Direct-Acting Antivirals in Patients with Genotype 1 Hepatitis C Virus Infection.
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Esposito I, Marciano S, Haddad L, Galdame O, Franco A, Gadano A, Flichman D, and Trinks J
- Subjects
- Adult, Aged, Amino Acid Substitution, Argentina, Female, Genotype, Hepacivirus drug effects, Hepacivirus genetics, Humans, Male, Middle Aged, Prevalence, Quasispecies, Sustained Virologic Response, Viral Nonstructural Proteins antagonists & inhibitors, Antiviral Agents therapeutic use, Drug Resistance, Viral, Hepatitis C, Chronic drug therapy, Viral Nonstructural Proteins genetics
- Abstract
This study aimed to assess the prevalence of natural resistance-associated substitutions (RASs) to NS3, NS5A and NS5B inhibitors in 86 genotype 1 Hepatitis C Virus (HCV)-infected patients from Buenos Aires, Argentina, and to determine their effect on therapy outcome. Additionally, virological, clinical and host genetic factors were explored as predictors of the presence of baseline RASs. NS3 RASs (39.2%) were more prevalent than NS5A RASs (25%) and NS5B RASs (8.9%). In the three regions, the frequencies of RASs were significantly higher in HCV-1b than in HCV-1a. The prevalence of Y93H, L159F and Q80K were 1.3%, 6.3% and 2.5%, respectively. IFNL3 CC genotype was identified as an independent predictor of the presence of baseline RASs in NS5A and NS3 genes ( p = 0.0005 and p = 0.01, respectively). Sustained virologic response was achieved by 93.3% of the patients after receiving direct-acting antivirals (DAAs), although 48.7% of them showed baseline RASs related to the DAA-regimen. Notably, the prevalence of clinically relevant RASs in the three genes was lower than that observed around the world. The baseline presence of RASs in both subtypes did not appear to affect therapy outcome. These results support the need to evaluate resistance patterns in each particular country since RASs´ prevalence significantly vary worldwide.
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- 2018
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32. Pharmacokinetic and pharmacodynamic evaluation of daclatasvir, asunaprevir plus beclabuvir as a fixed-dose co-formulation for the treatment of hepatitis C.
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Esposito I, Marciano S, and Trinks J
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- Administration, Oral, Antiviral Agents pharmacokinetics, Antiviral Agents pharmacology, Benzazepines administration & dosage, Benzazepines pharmacokinetics, Benzazepines pharmacology, Carbamates, Drug Combinations, Genotype, Hepacivirus isolation & purification, Hepatitis C virology, Humans, Imidazoles administration & dosage, Imidazoles pharmacokinetics, Imidazoles pharmacology, Indoles administration & dosage, Indoles pharmacokinetics, Indoles pharmacology, Isoquinolines administration & dosage, Isoquinolines pharmacokinetics, Isoquinolines pharmacology, Japan, Pyrrolidines, Sulfonamides administration & dosage, Sulfonamides pharmacokinetics, Sulfonamides pharmacology, Valine analogs & derivatives, Antiviral Agents administration & dosage, Hepacivirus genetics, Hepatitis C drug therapy
- Abstract
Introduction: Many reports have evaluated the clinical efficacy and safety of the fixed-dose all-oral combination of daclatasvir, asunaprevir, and beclabuvir (DCV-TRIO), which was approved in Japan in December 2016 for the treatment of hepatitis C genotype (GT)-1 infection. Areas covered: This article reviews the pharmacodynamic and pharmacokinetic properties of the DCV-TRIO combination. The topics covered include data regarding the drug's absorption, distribution, metabolism, excretion, and antiviral activity strategies. Its therapeutic efficacy and safety in GT-1 infection from phase 2/3 clinical trials are also discussed. Expert opinion: The ideal regimen for the treatment of Hepatitis C virus infection should be potent, pangenotypic, Ribavirin-free, safe, co-formulated, and affordable. Considering these characteristics, DCV-TRIO is neither pangenotypic nor potent enough against GT-1a, regardless of the presence or absence of cirrhosis. Other potential limitations of this regimen are its dosification (twice-daily), and the fact that since it includes a protease inhibitor, it is contraindicated in decompensated cirrhosis. For these reasons, it has only been approved in Japan, where more than 70% of the patients are infected with GT-1b. However, this co-formulation might still have a place in the treatment of non-cirrhotic patients infected with GT-1b provided that massive access to treatment is facilitated.
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- 2018
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33. Role of HLA-DP and HLA-DQ on the clearance of hepatitis B virus and the risk of chronic infection in a multiethnic population.
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Trinks J, Nishida N, Hulaniuk ML, Caputo M, Tsuchiura T, Marciano S, Haddad L, Blejer J, Bartoli S, Ameigeiras B, Frías SE, Vistarini C, Heinrich F, Remondegui C, Ceballos S, Echenique G, Charre Samman M, D'Amico C, Rojas A, Martínez A, Ridruejo E, Fernández RJ, Burgos Pratx L, Salamone H, Nuñez F, Galdame O, Gadano A, Corach D, Sugiyama M, Flichman D, Tokunaga K, and Mizokami M
- Subjects
- Adult, Aged, Argentina epidemiology, Chi-Square Distribution, Female, Gene Frequency, Genotype, HLA Antigens immunology, HLA-DP alpha-Chains genetics, HLA-DP alpha-Chains immunology, HLA-DP beta-Chains genetics, HLA-DP beta-Chains immunology, HLA-DQ Antigens genetics, HLA-DQ Antigens immunology, HLA-DQ beta-Chains genetics, HLA-DQ beta-Chains immunology, Hepatitis B virus immunology, Hepatitis B, Chronic ethnology, Hepatitis B, Chronic immunology, Hepatitis B, Chronic virology, Host-Pathogen Interactions, Humans, Linkage Disequilibrium, Logistic Models, Male, Middle Aged, Molecular Epidemiology, Multivariate Analysis, Odds Ratio, Phylogeny, Protective Factors, Risk Factors, HLA Antigens genetics, Hepatitis B virus genetics, Hepatitis B, Chronic genetics, Polymorphism, Single Nucleotide
- Abstract
Background & Aims: HBV infection exhibits geographical variation in its distribution in South America. While HBV rates are low in central Argentina, the north-western region exhibits intermediate HBV rates. Unfortunately, the reasons that could explain this difference are still unknown., Methods: A total of 1440 Argentines were recruited and grouped into HBV patients, HBV-resolved individuals and healthy controls. Genetic ancestry was assessed by analysis of biparental lineages and ancestry autosomal typing. SNPs of HLA-DPA1 (rs3077), HLA-DPB1 (rs9277542), HLA-DQB1 (rs2856718) and HLA-DQB2 (rs7453920) were determined, and HBV genotyping was performed by phylogenetic analysis in HBV patients., Results: Native American ancestry prevailed in the north-western region when compared with central Argentina (P<.0001). However, no differences were observed among the three groups of each region. The distribution of HBV genotypes revealed significant differences (P<.0001). Three SNPs (rs3077, rs9277542 and rs7453920) showed a significant association with protection against chronic HBV and viral clearance in both regions. The remaining SNP showed a significant association with susceptibility to chronic HBV. The frequency rates of rs3077-T, related to protection against chronic HBV and viral clearance, were lower in north-western Argentina when compared with central Argentina. The same uneven frequency rates were observed for SNP rs9277542., Conclusions: This is the first study addressing the associations between the HLA-DP and HLA-DQ loci and the protection against chronic HBV and viral clearance in a multiethnic South American population. The uneven distribution of HLA-DP and HLA-DQ supports the HBV epidemiological differences observed in these two regions of Argentina with dissimilar ancestry genetic background., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
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- 2017
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34. Increased prevalence of human herpesvirus type 8 (HHV-8) genome among blood donors from North-Western Argentina.
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Hulaniuk ML, Torres O, Bartoli S, Fortuny L, Burgos Pratx L, Nuñez F, Salamone H, Corach D, Trinks J, and Caputo M
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- Adult, DNA, Viral blood, Female, Humans, Male, Middle Aged, Polymerase Chain Reaction, Prevalence, Racial Groups, South America epidemiology, Young Adult, Blood Donors, Herpesviridae Infections epidemiology, Herpesvirus 8, Human isolation & purification
- Abstract
The prevalence of HHV-8 infection varies widely in South American populations, displaying geographical variations in its distribution. The heterogeneous genetic contributions provided by the transatlantic parental populations that modified the Native American genomes may explain this epidemiological observation. Aiming to determine the prevalence of HHV-8 genome among healthy South American blood donors and its potential association with genetic ancestry, 772 individuals were screened by a highly sensitive PCR protocol and ancestry was assessed in 414 samples. HHV-8 DNA was significantly more prevalent among North-western Argentines than among those from the metropolitan region (P = 0.001) and Bolivians (P = 0.0008), but no differences were found when compared with Peruvians and Paraguayans. Although significant differences were observed in the ancestry components of the studied populations, no association was found in the genetic admixture between HHV-8 [+] and HHV-8 [-] samples from the same place. These results support the hypothesis of the existence of geographical factors related to HHV-8 prevalence which could be explained by the presence of specific risk factors, cultural characteristics or behaviors, probably related to contaminated saliva and/or sexual transmission. The presence of HHV-8 in South American blood units available for transfusion and an increased risk of infection in some provinces of North-western Argentina represent a hazard for immunosuppressed recipients. J. Med. Virol. 89:518-527, 2017. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)
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- 2017
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35. Hepatitis C virus resistance to the new direct-acting antivirals.
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Esposito I, Trinks J, and Soriano V
- Subjects
- Drug Resistance, Viral, Hepacivirus genetics, Hepacivirus isolation & purification, Hepatitis C virology, Hepatitis C, Chronic drug therapy, Humans, Treatment Failure, Virus Replication, Antiviral Agents pharmacology, Hepacivirus drug effects, Hepatitis C drug therapy
- Abstract
Introduction: The treatment of hepatitis C virus (HCV) infection has dramatically improved in recent years with the widespread use of interferon-free combination regimens. Despite the high sustained virological response (SVR) rates (over 90%) obtained with direct-acting antivirals (DAAs), drug resistance has emerged as a potential challenge. The high replication rate of HCV and the low fidelity of its RNA polymerase result in a high degree of genetic variability in the HCV population, which ultimately explains the rapid selection of drug resistance associated variants (RAVs)., Areas Covered: Results from clinical trials and real-world experience have both provided important information on the rate and clinical significance of RAVs. They can be present in treatment-naive patients as natural polymorphisms although more frequently they are selected upon treatment failure. In patients engaged in high-risk behaviors, RAVs can be transmitted., Expert Opinion: Although DAA failures generally occur in less than 10% of treated chronic hepatitis C patients, selection of drug resistance is the rule in most cases. HCV re-treatment options are available, but first-line therapeutic strategies should be optimized to efficiently prevent DAA failure due to baseline HCV resistance. Considerable progress is being made and next-generation DAAs are coming with pangenotypic activity and higher resistance barrier.
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- 2016
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36. CSI-EPT: A Contrast Source Inversion Approach for Improved MRI-Based Electric Properties Tomography.
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Balidemaj E, van den Berg CA, Trinks J, van Lier AL, Nederveen AJ, Stalpers LJ, Crezee H, and Remis RF
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- Algorithms, Female, Humans, Models, Biological, Pelvis physiology, Image Processing, Computer-Assisted methods, Magnetic Resonance Imaging methods, Tomography methods
- Abstract
Electric properties tomography (EPT) is an imaging modality to reconstruct the electric conductivity and permittivity inside the human body based on B1(+) maps acquired by a magnetic resonance imaging (MRI) system. Current implementations of EPT are based on the local Maxwell equations and assume piecewise constant media. The accuracy of the reconstructed maps may therefore be sensitive to noise and reconstruction errors occur near tissue boundaries. In this paper, we introduce a multiplicative regularized CSI-EPT method (contrast source inversion-electric properties tomography) where the electric tissue properties are retrieved in an iterative fashion based on a contrast source inversion approach. The method takes the integral representations for the electromagnetic field as a starting point and the tissue parameters are obtained by iteratively minimizing an objective function which measures the discrepancy between measured and modeled data and the discrepancy in satisfying a consistency equation known as the object equation. Furthermore, the objective function consists of a multiplicative Total Variation factor for noise suppression during the reconstruction process. Finally, the presented implementation is able to simultaneously include more than one B1(+) data set acquired by complementary RF excitation settings. We have performed in vivo simulations using a female pelvis model to compute the B1(+) fields. Three different RF excitation settings were used to acquire complementary B1(+) fields for an improved overall reconstruction. Numerical results illustrate the improved reconstruction near tissue boundaries and the ability of CSI-EPT to reconstruct small tissue structures.
- Published
- 2015
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37. Influence of ethnicity on the distribution of genetic polymorphisms associated with risk of chronic liver disease in South American populations.
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Pontoriero AC, Trinks J, Hulaniuk ML, Caputo M, Fortuny L, Pratx LB, Frías A, Torres O, Nuñez F, Gadano A, Argibay P, Corach D, and Flichman D
- Subjects
- Alleles, Chronic Disease, Gene Frequency, Genotype, Humans, Male, Polymorphism, Single Nucleotide, Prevalence, Risk, Risk Factors, South America epidemiology, South America ethnology, Ethnicity genetics, Genetic Predisposition to Disease, Liver Diseases epidemiology, Liver Diseases etiology, Polymorphism, Genetic
- Abstract
Background: The global burden of chronic liver disease is rising. Besides environmental, behavioral, viral and metabolic factors, genetic polymorphisms in patatin-like phospholipase-3 (PNPLA3) and vitamin D receptor (VDR) genes have been related to the development of chronic liver disease and progression towards liver cancer. Although their prevalence differs remarkably among ethnic groups, the frequency of these polymorphisms in South American populations -whose genetic background is highly admixed- has been poorly studied. Hence, the aim of this study was to characterize polymorphisms related to chronic liver disease and their association with the genetic ancestry of South American populations., Results: DNA samples from 258 healthy unrelated male volunteers were analyzed. The frequencies of G and C alleles of rs738409 polymorphism (PNPLA3 gene) were 74 % and 26 %, respectively; whereas the bAt (CCA) haplotype (VDR gene) was observed in 32.5 % of the samples. The GG genotype of PNPLA3 rs738409 and the bAt (CCA) haplotype -associated with an increased risk of chronic liver disease and progression towards liver cancer- were significantly more frequent among samples exhibiting maternal and paternal Native American haplogroups (63.7 % and 64.6 %), intermediate among admixed samples (45.1 % and 44.9 %; p = 0.03) and the lowest for Non-native American ancestry (30.1 % and 29.6 %; p = 0.001 and p = 0.0008)., Conclusions: These results suggest that individuals with Native American ancestry might have a high risk of chronic liver disorders and cancer. Furthermore, these data not only support the molecular evaluation of ancestry in multi-ethnic population studies, but also suggest that the characterization of these variants in South American populations may be useful for establishing public health policies aimed at high risk ethnic communities.
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- 2015
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38. Pre-treatment prediction of response to peginterferon plus ribavirin in chronic hepatitis C genotype 3.
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Marciano S, Borzi SM, Dirchwolf M, Ridruejo E, Mendizabal M, Bessone F, Sirotinsky ME, Giunta DH, Trinks J, Olivera PA, Galdame OA, Silva MO, Fainboim HA, and Gadano AC
- Abstract
Aim: To evaluate pre-treatment factors associated with sustained virological response (SVR) in patients with hepatitis C virus (HCV) genotype 3 treated with peginterferon and ribavirin (RBV)., Methods: We retrospectively analyzed treatment naive, mono-infected HCV genotype 3 patients treated with peginterferon and RBV. Exclusion criteria included presence of other liver disease, alcohol consumption and African American or Asian ethnicity. The variables collected and compared between patients who achieved an SVR and patients who did not were as follows: gender, age, fibrosis stage, diabetes, body mass index, steatosis, INFL3 polymorphism, pre-treatment HCV-RNA, type of peginterferon, RBV dose and adherence., Results: A total of 107 patients treated between June, 2004 and March, 2013 were included. Mean treatment duration was 25.1 (± 1.8) wk. Overall, 58% (62/107) of the patients achieved an SVR and 42% (45/107) did not. In the multivariate logistic regression analysis, pre-treatment HCV-RNA ≥ 600000 UI/mL (OR = 0.375, 95%CI: 0.153-0.919, P = 0.032) and advanced fibrosis (OR = 0.278, 95%CI: 0.113-0.684, P = 0.005) were significantly associated with low SVR rates. In patients with pre-treatment HCV-RNA ≥ 600000 UI/mL and advanced fibrosis, the probability of achieving an SVR was 29% (95%CI: 13.1-45.2). In patients with pre-treatment HCV-RNA < 600000 UI/mL and mild to moderate fibrosis, the probability of achieving an SVR was 81% (95%CI: 68.8-93.4)., Conclusion: In patients with HCV genotype 3 infections the presence of advance fibrosis and high pre-treatment viral load might be associated with poor response to peginterferon plus RBV. These patients could benefit the most from new direct antiviral agents-based regimes.
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- 2015
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39. Human pegivirus molecular epidemiology in Argentina: potential contribution of Latin American migration to genotype 3 circulation.
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Trinks J, Maestri M, Oliveto F, Del Pino N, Weissenbacher M, Torres OW, and Oubiña JR
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- Adult, Argentina epidemiology, Cluster Analysis, Disease Transmission, Infectious, Female, Flaviviridae isolation & purification, Flaviviridae Infections transmission, Genotype, Humans, Infectious Disease Transmission, Vertical, Male, Molecular Epidemiology, Molecular Sequence Data, Phylogeny, Pregnancy, RNA, Viral genetics, Sequence Analysis, DNA, Sequence Homology, Young Adult, Flaviviridae classification, Flaviviridae genetics, Flaviviridae Infections epidemiology, Flaviviridae Infections virology, Human Migration
- Abstract
In order to determine the human pegivirus (HPgV) genotypic diversity in Argentina taking into account the potential contribution of human migration from neighboring countries, samples from 130 Argentine injecting drug users, 116 Argentine- and 50 immigrant-pregnant women were analyzed. HPgV RNA prevalence among human immunodeficiency virus (HIV)-positive injecting drug users was similar to HIV-positive pregnant women, as was the case when comparing HIV-negative injecting drug users and HIV-negative pregnant women (P > 0.05). HPgV genotype 2 (HPgV/2) was prevalent among both Argentine injecting drug users and pregnant women, in contrast to HPgV/3 observed among pregnant women from Latin American countries with predominant indigenous populations and who had experienced their initial sexual intercourses--and possibly their source of infection--in those countries (P < 0.01). In addition, HPgV vertical and horizontal transmission was proven by molecular analysis of E2 gene and construction of identity matrixes with epidemiologically non-related isolates. This study shows that human migration from neighboring Latin American countries with predominant indigenous populations might contribute to HPgV/3 circulation in Argentina., (© 2014 Wiley Periodicals, Inc.)
- Published
- 2014
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40. In vitro replication competence of a hepatitis B genotype D/A recombinant virus: dissimilar biological behaviour regarding its parental genotypes.
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Trinks J, Sugiyama M, Tanaka Y, Kurbanov F, Benetucci J, Giménez E, Weissenbacher MC, Mizokami M, and Oubiña JR
- Subjects
- Argentina, Base Sequence, DNA, Viral blood, DNA, Viral isolation & purification, Genotype, Hepatitis B e Antigens blood, Hepatitis B virus classification, Hepatitis B virus genetics, Hepatitis B, Chronic virology, Humans, Molecular Sequence Data, Sequence Analysis, DNA, Hepatitis B virus physiology, Recombination, Genetic, Virus Replication
- Abstract
Hepatitis B virus (HBV) DNA recombinants contribute to ~30% of the overall full-length sequences already deposited in GenBank. However, their biological behaviour has not been analysed so far. In this study, the in vitro replication kinetics of the first D/A recombinant from the American continent differed from its parental genotypes, exhibiting higher extracellular levels of HBV DNA and hepatitis B e antigen. Southern blots of intracellular core-associated HBV DNA were in agreement with such results. Because this recombinant was obtained from an Argentinian injecting drug user belonging to a vulnerable community, these results are of singular relevance for regional public health. Further in vivo studies are urgently needed to determine the pathogenicity of these replicative competent clones.
- Published
- 2013
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41. Naturally occurring hepatitis B virus (HBV) variants with primary resistance to antiviral therapy and S-mutants with potential primary resistance to adefovir in Argentina.
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Cuestas ML, Rivero CW, Minassian ML, Castillo AI, Gentile EA, Trinks J, León L, Daleoso G, Frider B, Lezama C, Galoppo M, Giacove G, Mathet VL, and Oubiña JR
- Subjects
- Adenine pharmacology, Adolescent, Adult, Argentina, Child, Child, Preschool, Female, Genotype, Hepatitis B virus classification, Hepatitis B virus genetics, Hepatitis B virus isolation & purification, Hepatitis B, Chronic drug therapy, Humans, Male, Middle Aged, Retrospective Studies, Adenine analogs & derivatives, Antiviral Agents pharmacology, Drug Resistance, Viral, Hepatitis B Surface Antigens genetics, Hepatitis B virus drug effects, Hepatitis B, Chronic virology, Mutation, Missense, Organophosphonates pharmacology
- Abstract
Hepatitis B virus (HBV) variants may either emerge in patients with chronic hepatitis B (CHB) as a result of positive selection pressure exerted by their own immune response, or during therapy with nucleos(t)ide analogues (NAs). Naturally occurring HBV variants with primary antiviral resistance are rarely observed. The aim of this study was to retrospectively analyze the (eventual) circulation of HBV variants with natural resistance to NAs currently used as therapy for CHB in Argentina. This study reports 13 cases of CHB-infected patients with natural antiviral resistance to at least one NA. Five of them were also carriers of S-variants that might escape the humoral immune system recognition with potential resistance to adefovir. In addition to the already reported A2 HBV subgenotype association to NAs natural resistance, E and F genotypes association to such resistance is described for the first time. These findings suggest that sequence analysis of the HBV reverse transcriptase might be an essential tool before starting antiviral therapy, in order to choose the proper NAs for optimizing the therapeutic management of chronically infected patients. Moreover, the circulation and transmission of S-mutants with resistance to such antiviral drugs should be of public health concern as they may represent an additional risk for the community., (2010 Elsevier B.V. All rights reserved.)
- Published
- 2010
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42. Detection of hepatitis B virus (HBV) genotype E carried--even in the presence of high titers of anti-HBs antibodies--by an Argentinean patient of African descent who had received vaccination against HBV.
- Author
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Mathet VL, Cuestas ML, Ruiz V, Minassian ML, Rivero C, Trinks J, Daleoso G, León LM, Sala A, Libellara B, Corach D, and Oubiña JR
- Subjects
- Adolescent, Adult, Argentina, Black People, Carrier State virology, Child, Preschool, Female, Genotype, Hepatitis B immunology, Hepatitis B prevention & control, Hepatitis B virology, Hepatitis B Surface Antigens genetics, Hepatitis B Vaccines administration & dosage, Hepatitis B virus genetics, Humans, Mutation, Phylogeny, Vaccination, Hepatitis B Antibodies blood, Hepatitis B Surface Antigens immunology, Hepatitis B virus classification, Hepatitis B virus isolation & purification
- Abstract
Genotype E hepatitis B virus (HBV) was detected in two Argentine sisters exhibiting an African mitochondrial lineage. One of them (who had been vaccinated against HBV) exhibited anti-HBs cocirculating antibodies without HBsAg escape mutants, while her unvaccinated sister showed a D144A HBsAg escape mutant without anti-HBs antibodies. Both sisters carried an unusual L209V substitution within HBsAg.
- Published
- 2006
- Full Text
- View/download PDF
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