Identification of N-terminal protein acetylation and arginine methylation of the voltage-gated sodium channel in end-stage heart failure human heart

The α subunit of the cardiac voltage-gated sodium channel, Naᵥ1.5, provides the rapid sodium inward current that initiates cardiomyocyte action potentials. Here, we analyzed for the first time the post-translational modifications of Naᵥ1.5 purified from end-stage heart failure human cardiac tissue. We identified R526 methylation as the major post-translational modification of any Naᵥ1.5 arginine or lysine residue. Unexpectedly, we found that the N terminus of Naᵥ1.5 was: 1) devoid of the initiation methionine, and 2) acetylated at the resulting initial alanine residue. This is the first evidence for N-terminal acetylation in any member of the voltage-gated ion channel superfamily. Our results open the door to explore Naᵥ1.5 N-terminal acetylation and arginine methylation levels as drivers or markers of end-stage heart failure

Evaluation of bias in HIV seroprevalence estimates from national household surveys

Submitted by Gilvan Almeida ([email protected]) on 2016-12-07T12:03:30Z No. of bitstreams: 2 license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) FieldEvaluation.pdf: 177639 bytes, checksum: 417e97b6da6816379d956c2c88c54fef (MD5)Rejected by Éder Freyre ([email protected]), reason: Refazer on 2017-02-14T16:35:23Z (GMT)Submitted by Gilvan Almeida ([email protected]) on 2019-02-06T16:28:18Z No. of bitstreams: 2 FieldEvaluation.pdf: 177639 bytes, checksum: 417e97b6da6816379d956c2c88c54fef (MD5) license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5)Approved for entry into archive by Regiane Silva ([email protected]) on 2019-08-26T13:12:58Z (GMT) No. of bitstreams: 2 FieldEvaluation.pdf: 177639 bytes, checksum: 417e97b6da6816379d956c2c88c54fef (MD5) license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5)Made available in DSpace on 2019-08-26T13:12:58Z (GMT). No. of bitstreams: 2 FieldEvaluation.pdf: 177639 bytes, checksum: 417e97b6da6816379d956c2c88c54fef (MD5) license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) Previous issue date: 2008Fundação Alfredo da Matta. Manaus, AM, Brasil.London School of Hygiene & Tropical Medicine. London, UK.Fundação Alfredo da Matta. Manaus, AM, Brasil.Fundação Alfredo da Matta. Manaus, AM, Brasil.Fundação Alfredo da Matta. Manaus, AM, Brasil.Fundação Oswaldo Cruz. Escola Nacional de Saúde Pública Sergio Arouca. Rio de Janeiro, RJ, Brasil.World Health Organization. Geneva, Switzerland.OBJECTIVES: To assess the performance, usefulness and cost of a rapid treponemal antibody assay (VisiTect Syphilis) to detect syphilis in high risk populations. METHODS: People who attended STI clinics in Manaus, Brazil, were screened for syphilis using the fluorescent treponemal antibody absorption (FTA-Abs) test and a non-treponemal test (Venereal Diseases Research Laboratory (VDRL)), and for HIV. Finger prick blood samples were tested with VisiTect Syphilis. The rapid test was evaluated against the reference FTA-Abs and for its usefulness in detecting active syphilis (FTA-Abs and VDRL positive). Operational performance was assessed through providers' and patients' interviews. An economic evaluation was conducted from the provider's perspective. RESULTS: 510 patients (60% men) were enrolled, of whom 13 (2.5%) were HIV-1 seropositive. Syphilis prevalence (FTA-Abs) was 18% and active syphilis prevalence was 7.5%. 11% (57/506) of samples were positive by VisiTect. The sensitivity, specificity, positive and negative predictive values of VisiTect Syphilis were 57% (95% CI 45.8 to 66.7), 99% (95% CI 97.0 to 99.6), 91% (95% CI 80.0 to 96.7) and 91% (95% CI 88.0 to 93.5), respectively. VisiTect Syphilis identified 79% (30/38) of active syphilis cases. The cost per case of syphilis was $16.8 for VDRL,$33.2 for low cost and $56.3 for high cost VisiTect Syphilis; the cost per case of active syphilis was$21.3, $57.5 and$97.6, respectively. Patients identified finger prick pain and preference for venous blood collection as minor barriers to test use. CONCLUSION: VisiTect Syphilis had low sensitivity in field use and was less cost effective than conventional VDRL. However, rapid and correct identification of a high proportion of active syphilis cases combined with operational characteristics suggest a role in high risk populations

Proteomic Studies on the Management of High-Grade Serous Ovarian Cancer Patients: A Mini-Review

Teixit cancerígen; Càncer d'ovaris; ProteòmicaTejido canceroso; Cáncer de ovarios; ProteómicaCancer tissue; Ovarian cancer; ProteomicsHigh-grade serous ovarian cancer (HGSC) remains the most common and deadly subtype of ovarian cancer. It is characterized by its late diagnosis and frequent relapse despite standardized treatment with cytoreductive surgery and platinum-based chemotherapy. The past decade has seen significant advances in the clinical management and molecular understanding of HGSC following the publication of the Cancer Genome Atlas (TCGA) researchers and the introduction of targeted therapies with anti-angiogenic drugs and poly(ADP-ribose) polymerase inhibitors in specific subgroups of patients. We provide a comprehensive review of HGSC, focusing on the most important molecular advances aimed at providing a better understanding of the disease and its response to treatment. We emphasize the role that proteomic technologies are now playing in these two aspects of the disease, through the identification of proteins and their post-translational modifications in ovarian cancer tumors. Finally, we highlight how the integration of proteomics with genomics, exemplified by the work performed by the Clinical Proteomic Tumor Analysis Consortium (CPTAC), can guide the development of new biomarkers and therapeutic targets.This work was supported by the PhD4MD collaborative research program between the Vall d’Hebron Research Institute (VHIR) and the Centre for Genomic Regulation (CRG). The CRG/UPF Proteomics Unit is part of the Spanish Infrastructure for Omics Technologies (ICTS OmicsTech) and it is a member of the ProteoRed PRB3 consortium which is supported by grant PT17/0019 of the PE I + D + i 2013–2016 from the Instituto de Salud Carlos III (ISCIII) and ERDF. We acknowledge support from the Spanish Ministry of Science and Innovation (CTQ2016-80364-P) and “Centro de Excelencia Severo Ochoa 2013–2017”, SEV-2012-0208; the “Secretaria d’Universitats i Recerca del Departament d’Economia i Coneixement de la Generalitat de Catalunya” (2017SGR595 and 2017SGR1661), from the Instituto de Salud Carlos III (PI15/02238, PI18/01017, CPII18/00027) and from the Ministerio de Economia y Competitividad y Fondos FEDER (RTC-2015-3821). We also acknowledge the support of the Spanish Ministry of Science and Innovation to the EMBL partnership, the Centro de Excelencia Severo Ochoa and the CERCA Programme/Generalitat de Catalunya

Point-of-care screening for syphilis and HIV in the borderlands: challenges in implementation in the Brazilian Amazon.

BACKGROUND: Point-of-care (POC) screening for HIV and syphilis using rapid testing was implemented in indigenous communities in the triple-border area of the Brazilian Amazon. We describe the context of the early introduction of POC screening, explore hindering and enabling factors for POC implementation, and recommend strategies for feasible, viable, and sustainable syphilis and HIV screening interventions. METHODS: This was a qualitative study based on grounded theory methodology. Data were collected using in-depth interviews, semi-structured questionnaires, and field observations and were analysed using the framework approach. Qualitative information was complemented by quantitative data for descriptive purposes. RESULTS: An overall high score for vulnerability to acquiring HIV and syphilis was observed among the indigenous communities. Health professionals reported satisfactory rapid testing acceptance, although concerns were raised about the pain of the fingerprick. Counselling-related challenges included ensuring the accuracy of translations, collaborating with translators and communicating positive test results. Over 3 months, 86.7% of the syphilis-positive individuals began treatment, and all of them notified their partners. Accessibility, measured as travel time via the local transportation network, was a barrier to health care access. A lack of gasoline for boats and other transportation was also a hindering factor at all levels of implementation. CONCLUSIONS: The recommendations address the preparation phase at the coordination level as well as at the training level. Tools such as strengths, weaknesses, opportunities, and threats (SWOT) analyses; checklists; context-adapted protocols; and fact sheets are very simple methods to facilitate implementation. The findings of this study are important because they may inform the implementation of new health technologies in low-resource national disease control programmes in remote communities

Rapid Point-of-Care Diagnostic Test for Syphilis in High-Risk Populations, Manaus, Brazil

We assessed the acceptability and operational suitability of a rapid point-of-care syphilis test and identified barriers to testing among high-risk groups and healthcare professionals in a sexually transmitted infections clinic in Manaus, Brazil. Use of this test could considerably alleviate the impact of syphilis in hard-to-reach populations in the Amazon region of Brazil

HIV and syphilis in the context of community vulnerability among indigenous people in the Brazilian Amazon.

BACKGROUND: Contextual factors shape the risk of acquiring human immunodeficiency virus (HIV) and syphilis. We estimated the prevalence of both infections among indigenous people in nine indigenous health districts of the Brazilian Amazon and examined the context of community vulnerability to acquiring these infections. METHODS: We trained 509 health care workers to screen sexually active populations in the community for syphilis and HIV using rapid testing (RT). We then assessed the prevalence of HIV and syphilis using RT. A multivariable analysis was used to identify factors associated with syphilis infection (sociodemographic, condom use, intrusion, population mobility, and violence). RESULTS: Of the 45,967 indigenous people tested, the mean age was 22.5 years (standard deviation: 9.2), and 56.5% were female. Overall, for HIV, the prevalence was 0.13% (57/43,221), and for syphilis, the prevalence was 1.82% (745/40,934). The prevalence in men, women, and pregnant women for HIV was 0.16%, 0.11%, and 0.07%, respectively, and for syphilis, it was 2.23%, 1.51%, and 1.52%, respectively. The district Vale do Javari had the highest prevalence of both infections (HIV: 3.38%, syphilis: 1.39%). This district also had the highest population mobility and intrusion and the lowest availability of prenatal services. Syphilis infection was independently associated with age (odds ratio [OR] 1.04, 95% confidence interval [CI]: 1.03-1.05), male sex (OR 1.32, 95% CI: 1.14-1.52), and mobility (moderate: OR: 7.46, 95% CI: 2.69-20.67; high: OR 7.09, 95% CI: 3.79-13.26). CONCLUSIONS: The large-scale integration of RT in remote areas increased case detection among pregnant women, especially for syphilis, in districts with higher vulnerability. Mobility is an important risk factor, especially in districts with higher vulnerability. Contextually appropriate approaches that address this factor could contribute to the long-term success of HIV and syphilis control programs

Antimicrobial resistance in Neisseria gonorrhoeae isolates from foreign-born population in the European Gonococcal Antimicrobial Surveillance Programme

International spread has contributed substantially to the high prevalence of antimicrobial resistant (AMR) Neisseria gonorrhoeae infections worldwide. We compared the prevalence of AMR gonococcal isolates among native persons to foreign-born (reporting country different from country of birth) persons, and describe the epidemiological and clinical characteristics of foreign-born patients and their associations to AMR. We analysed isolates and patient data reported to the European Gonococcal Antimicrobial Surveillance Programme (Euro-GASP) 2010-2014 (n=9529). Forty-three per cent of isolates had known country of birth and 17.2% of these were from persons born abroad. Almost 50% of foreign-born were from the WHO European Region (13.1% from non-European Union [EU] and the European Economic Area [EEA] countries). Compared with isolates from natives, isolates from foreign-born had a similar level (p>0.05) of azithromycin resistance (7.5% vs 7.2%), ciprofloxacin resistance (50.0% vs 46.3%) and of decreased susceptibility to ceftriaxone (1.9% vs 2.8%); a lower rate of cefixime resistance (5.7% vs 3.6%, p=0.02), and a higher proportion of isolates producing penicillinase (8.4% vs 11.7%, p=0.02). Among isolates from persons born outside EU/EEA, the level of decreased susceptibility to ceftriaxone was higher (1.8% vs 3.5%, p=0.02), particularly in those from the WHO Eastern Mediterranean Region and non-EU/EEA WHO European countries (1.9% vs 9.6% and 8.7%, respectively, p<0.01). In multivariable analysis, foreign-born patients with AMR isolates were more likely to be from non-EU/EEA WHO European countries (adjusted OR [aOR]: 3.2, 95% CI 1.8 to 5.8), WHO Eastern Mediterranean countries (aOR: 1.8, 95% CI 1.1 to 3.3) and heterosexual males (aOR: 1.8, 95% CI 1.2 to 2.7). Importation of AMR strains remains an important threat in the EU/EEA. Research to improve understanding of sexual networks within foreign born and sexual tourism populations could help to inform effective tailor-made interventions. The Euro-GASP demonstrates the public health value of quality-assured surveillance of gonococcal AMR and the need for strengthened AMR surveillance, particularly in the non-EU/EEA WHO European Region

Sistema d'informació big data basat en Apache Kylin

Actualment hi ha una gran quantitat de dades i cada cop disposem d'un temps menor per analitzar-la. Les dades són informació important per a la presa de decisions. Els sistemes d'informació basats en Business Intelligence ens proporcionen la solució als problemes que ens generen la gran quantitat de dades i l'absència de temps. Aquest projecte és una solució a aquests problemes tècnics i a la necessitat de substituir les solucions actuals, que amb el pas del temps i l'augment de volum de dades han vist afectades el seu rendiment. La solució proposada pren com a referència una solució implentada per a un client de l'empresa Pos Potential que actualment dona resposta als problemes plantejats, però cal donar una resposta al nou volum de dades. El sistema disposa d'un clúster distribuït de Hadoop realitzat amb màquines Debian, d'una ETL, un club de dades OLAP i d'un informe Excel per consultar les dades.Actualmente hay una gran cantidad de datos y cada vez disponemos de un tiempo menor para analizarla. Los datos son información importante para la toma de decisiones. Los sistemas de información basados en Business Intelligence nos proporcionan la solución a los problemas que nos generan la gran cantidad de datos y la ausencia de tiempo. Este proyecto es una solución a estos problemas técnicos y a la necesidad de substituir las soluciones actuales, que con el paso del tiempo y el aumento del volumen de datos han visto afectados su rendimiento. La solución propuesta toma como referencia una solución implementada para una cliente de la empresa Pos Potential que actualmente da respuesta a los problemas planteados, aunque es necesaria una respuesta al nuevo volumen de datos. El sistema dispone de un cluster distribuido de Hadoop realizado con máquinas Debian, de una ETL, un club de datos OLAP y de un informe Excel para consultar los datos.Nowadays there is a large amount of data and every time we have less time to analyze it. Data are important information for decision making. The information Systems based on Business Intelligence provide us with the solution to the problemes generated by the large amount of data and the absence of time. This project is a solution to these technical problems and to the need to replace the corrent solutions, which over time and the increase in volume of data have been affected by their performance. The solution proposed takes as a reference a solution implemented for a Pos Potential company client that currently responds to the problems proposed, but we must respond to the new volume of data. The system has a distributed Hadoop clúster made with Debian Machines, an ETL, an OLAP cube and an Excel report to consult data

identifying patients with relapsing remitting multiple sclerosis using algorithms applied to us integrated delivery network healthcare data

Abstract Background Relapsing-remitting multiple sclerosis (RRMS) has a major impact on affected patients; therefore, improved understanding of RRMS is important, particularly in the context of real-world evidence. Objectives To develop and validate algorithms for identifying patients with RRMS in both unstructured clinical notes found in electronic health records (EHRs) and structured/coded health care claims data. Methods US Integrated Delivery Network data (2010–2014) were queried for study inclusion criteria (possible multiple sclerosis [MS] base cohort): one or more MS diagnosis code, patients aged 18 years or older, 1 year or more baseline history, and no other demyelinating diseases. Sets of algorithms were developed to search narrative text of unstructured clinical notes (EHR clinical notes–based algorithms) and structured/coded data (claims-based algorithms) to identify adult patients with RRMS, excluding patients with evidence of progressive MS. Medical records were reviewed manually for algorithm validation. Positive predictive value was calculated for both EHR clinical notes–based and claims-based algorithms. Results From a sample of 5308 patients with possible MS, 837 patients with RRMS were identified using only the EHR clinical notes–based algorithms and 2271 patients were identified using only the claims-based algorithms; 779 patients were identified using both algorithms. The positive predictive value was 99.1% (95% confidence interval [CI], 94.2%–100%) for the EHR clinical notes–based algorithms and 94.6% (95% CI, 89.1%–97.8%) to 94.9% (95% CI, 89.8%–97.9%) for the claims-based algorithms. Conclusions The algorithms evaluated in this study identified a real-world cohort of patients with RRMS without evidence of progressive MS that can be studied in clinical research with confidence