28 research outputs found

    Follow-Up Study Confirms the Presence of Gastric Cancer DNA Methylation Hallmarks in High-Risk Precursor Lesions

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    Intestinal metaplasia confers an increased risk of progression to gastric cancer. However, some intestinal metaplasia patients do not develop cancer. The development of robust molecular biomarkers to stratify patients with advanced gastric precursor lesions at risk of cancer progression will contribute to guiding programs for prevention. Starting from a genome-wide methylation study, we have simplified the detection method regarding candidate-methylation tests to improve their applicability in the clinical environment. We identified CpG methylation at the ZNF793 and RPRM promoters as a common event in intestinal metaplasia and intestinal forms of gastric cancer. Furthermore, we also showed that Helicobacter pylori infection influences DNA methylation in early precursor lesions but not in intestinal metaplasia, suggesting that therapeutic strategies to prevent epigenome reprogramming toward a cancer signature need to be adopted early in the precursor cascade. To adopt prevention strategies in gastric cancer, it is imperative to develop robust biomarkers with acceptable costs and feasibility in clinical practice to stratified populations according to risk scores. With this aim, we applied an unbiased genome-wide CpG methylation approach to a discovery cohort composed of gastric cancer (n = 24), and non-malignant precursor lesions (n = 64). Then, candidate-methylation approaches were performed in a validation cohort of precursor lesions obtained from an observational longitudinal study (n = 264), with a 12-year follow-up to identify repression or progression cases. H. pylori stratification and histology were considered to determine their influence on the methylation dynamics. As a result, we ascertained that intestinal metaplasia partially recapitulates patterns of aberrant methylation of intestinal type of gastric cancer, independently of the H. pylori status. Two epigenetically regulated genes in cancer, RPRM and ZNF793, consistently showed increased methylation in intestinal metaplasia with respect to earlier precursor lesions. In summary, our result supports the need to investigate the practical utilities of the quantification of DNA methylation in candidate genes as a marker for disease progression. In addition, the H. pylori-dependent methylation in intestinal metaplasia suggests that pharmacological treatments aimed at H. pylori eradication in the late stages of precursor lesions do not prevent epigenome reprogramming toward a cancer signature

    7th Drug hypersensitivity meeting: part two

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    Pasados y presente. Estudios para el profesor Ricardo García Cárcel

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    Ricardo García Cárcel (Requena, 1948) estudió Historia en Valencia bajo el magisterio de Joan Reglà, con quien formó parte del primer profesorado de historia moderna en la Universidad Autónoma de Barcelona. En esta universidad, desde hace prácticamente cincuenta años, ha desarrollado una extraordinaria labor docente y de investigación marcada por un sagaz instinto histórico, que le ha convertido en pionero de casi todo lo que ha estudiado: las Germanías, la historia de la Cataluña moderna, la Inquisición, las culturas del Siglo de Oro, la Leyenda Negra, Felipe II, Felipe V, Austrias y Borbones, la guerra de la Independencia, la historia cultural, los mitos de la historia de España... Muy pocos tienen su capacidad para reflexionar, ordenar, analizar, conceptualizar y proponer una visión amplia y llena de matices sobre el pasado y las interpretaciones historiográficas. A su laboriosidad inimitable se añade una dedicación sin límites en el asesoramiento de alumnos e investigadores e impulsando revistas, dosieres, seminarios o publicaciones colectivas. Una mínima correspondencia a su generosidad lo constituye este volumen a manera de ineludible agradecimiento

    The value of colonoscopy to assess rectal bleeding in patients referred from Primary Care Units Utilidad de la colonoscopia en pacientes derivados desde Atención Primaria por rectorragia

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    Objectives: rectal bleeding is very common in the general population. It is produced mainly because of benign disease originating in the anus and the rectum. Our aim was to evaluate the need for colonoscopy in patients presenting with rectal bleeding. Patients and methods: patients referred from Primary Care Units and complaining of rectal bleeding were included prospectively in a three-month study. All patients underwent a careful medical history along with physical examination, laboratory tests, and colonoscopy. Results: 126 patients with a mean age of 49.2 years (range: 19-80) were studied. Rectal digital examination was abnormal in 75 cases (59.5%). Severe disease was encountered in 22 patients (neoplasm, angiodysplasia, and inflammatory bowel disease); 10 patients had polyps, 6 had colorectal cancer, and 6 had inflammatory bowel disease. Out of 63 patients younger than 50 years, 5 had severe disease, all of them in the form of inflammatory bowel disease. Conclusions: a neoplasm of the rectum and colon in patients younger than 50 years is a rare event. A colonoscopy must be performed in this group of patients to rule out inflammatory bowel disease.Objetivos: la rectorragia es frecuente en la población general. En la mayoría de las ocasiones está producida por patología anorrectal benigna. Nuestro objetivo era determinar la necesidad de realizar pruebas endoscópicas en pacientes con rectorragia. Pacientes y métodos: se incluyeron de forma prospectiva durante tres meses todos los pacientes que eran derivados desde la Atención Primaria por rectorragia. En todos los pacientes se realizó historia clínica y exploración física que incluía tacto rectal, analítica básica y una colonoscopia. Resultados: se incluyeron 126 pacientes con una edad media de 49,2 años (19-80). El tacto rectal fue anormal en 75 (59,5%). En 22 pacientes se encontró patología severa o positiva (lesiones neoplásicas, angiodisplasias y enfermedad inflamatoria intestinal); 10 pacientes pólipos, en 6 cáncer colorrectal y en 6 enfermedad inflamatoria intestinal. De los 63 pacientes menores de 50 años, 5 presentaron patología severa todos ellos con enfermedad inflamatoria intestinal. Conclusiones: la patología neoplásica en menores de 50 años con rectorragia es rara. Se debe realizar una rectoscopia en este grupo de edad para descartar una enfermedad inflamatoria intestinal

    A comprehensive update of the status of hepatitis C virus (HCV) infection in Mexico—A systematic review and meta-analysis (2008–2019)

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    Introduction and objectives: HCV infection is targeted by the WHO’s Global Health Sector Strategy on Viral Hepatitis to be reduced notably by 2030. However, renovated epidemiological data is needed to line up with such goals. Herein, we provide an updated review of incidence, prevalence, genotypes (GTs), and risk factors (RFs) of HCV infection in Mexico to build elimination strategies. Material and methods: HCV incidence was charted using the cumulative new cases/year at week 52. Prevalence, GTs, and RFs data from low-risk (LR-G) and high-risk (HR-Gs) groups were searched in PubMed/MEDLINE/Medigraphic/Scielo databases from January 2008 to December 2019 as per PRISMA guidelines. Weighted mean prevalence (WMP) was estimated; GTs and RFs were registered. Results: In this study, 25,247 new cases were reported. Ten states accumulated 76.32% of HCV incidence that peaked in men at 50–59 years and women at 60–64 years. Thirty-four studies revealed a WMP between 0.774%–2.5% in LR-Gs and 11.8%–39.6% in HR-Gs that included mainly prison inmates, drug users, and dialyzed patients. GT1 and GT2 were predominant; GT3a emerged. Subtypes 1a and 1b circulate differentially, whereas novel GT2 subtypes appeared. Unsafe blood transfusion was infrequent in younger groups, but parenteral/intravenous transmission through drug-related risk behaviors has arisen. Conclusions: HCV transmission increased notably among LR-Gs and HR-Gs in Mexico. Novel genotypes/subtypes emerged as well as risky behavioral routes of transmission. A national elimination strategy will require pro-active screening in designated risk groups, research in molecular epidemiology, medical training, robust epidemiological databases, and antiviral treatment available to all eligible HCV-infected patients

    Analytical and Clinical Performance of the CDC Real Time RT-PCR Assay for Detection and Typing of Dengue Virus

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    <div><p>Dengue is an acute illness caused by the positive-strand RNA dengue virus (DENV). There are four genetically distinct DENVs (DENV-1–4) that cause disease in tropical and subtropical countries. Most patients are viremic when they present with symptoms; therefore, RT-PCR has been increasingly used in dengue diagnosis. The CDC DENV-1–4 RT-PCR Assay has been developed as an <i>in-vitro</i> diagnostic platform and was recently approved by the US Food and Drug Administration (FDA) for detection of dengue in patients with signs or symptoms of mild or severe dengue. The primers and probes of this test have been designed to detect currently circulating strains of DENV-1–4 from around the world at comparable sensitivity. In a retrospective study with 102 dengue cases confirmed by IgM anti-DENV seroconversion in the convalescent sample, the RT-PCR Assay detected DENV RNA in 98.04% of the paired acute samples. Using sequencing as a positive indicator, the RT-PCR Assay had a 97.92% positive agreement in 86 suspected dengue patients with a single acute serum sample. After extensive validations, the RT-PCR Assay performance was highly reproducible when evaluated across three independent testing sites, did not produce false positive results for etiologic agents of other febrile illnesses, and was not affected by pathological levels of potentially interfering biomolecules. These results indicate that the CDC DENV-1–4 RT-PCR Assay provides a reliable diagnostic platform capable for confirming dengue in suspected cases.</p></div

    Limit of detection.

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    <p>The limit of detection of the Assay was evaluated by detection and quantification of (8) ten-fold dilutions of laboratory-adapted DENV-1–4 strains, 5 replicas per dilution. The Assay was performed in singleplex <b>(A)</b> and multiplex formats <b>(B)</b>. Viral RNA concentration was quantified using a standard curve measured in genome copy equivalents per milliliter of serum or plasma (GCE/mL). A linear regression was estimated for dilutions of virus stocks in plasma (dashed lines) or serum (solid line). Regression coefficient (R<sup>2</sup>) is shown for each serotype. Error bars indicate standard deviation of measurements from 5 replicas in GCE/mL.</p

    Comparison of published and oligonucleotides used in CDC DENV-1–4 Real Time RT-PCR Assay.

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    <p>Note: The sequences of the primers and probes of CDC DENV-1-4 RT-PCR Assay for detection of DENV-1-4 are covered under a pending patent application.</p>*<p>Frequency: number of complete sequence perfect matches over the total number of sequences screened.</p
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