Impact of patatin-like phospholipase domain-containing 3 gene polymorphism (rs738409) on severity of liver disease in HIV/hepatitis C virus-coinfected patients

Objective: To analyze the association between patatin-like phospholipase domain-containing 3 gene (PNPLA3) rs738409 polymorphism and severity of liver disease in HIV/hepatitis C virus-coinfected patients. Methods: We performed a cross-sectional study of 215 patients who underwent a liver biopsy. PNPLA3 rs738409 polymorphism was genotyped using GoldenGate assay. The outcome variables were as follows: advanced fibrosis (F ≥3 and FIB-4 ≥3.25), rapid fibrosis progression (FPR ≥0.10 fibrosis units/year), severe activity grade (A≥3), and steatosis (fatty hepatocytes ≥10%). The genetic association analysis was carried out according to an additive genetic model through logistic regressions adjusted by the most significant covariables. Results: Overall, 21.4% had F at least 3, 8.9% had FIB-4 at least 3.25, 11.4% had A at least 3, 60.6% had steatosis, and 32.5% had FPR at least 0.10. For each rs738409 G allele, we found an increased frequency of patients with advanced fibrosis (F at least 3) (0% CC, 18.5% CG, and 25.2% GG; P = 0.049) and FIB-4 at least 3.25 (0% CC, 3.8% CG, and 13.2% GG; P = 0.016). Furthermore, for each rs738409 G allele, the odds of having F at least 3 increased 2.15 times (95% confidence interval=1.07; 4.35; P = 0.029) and having FIB-4 at least 3.25 increased 8.77 times (95% of confidence interval = 1.11; 69.0; P = 0.039). Note that rs738409 G allele carriers tended to higher likelihood of having FPR at least 0.10, but statistical significance was not reached (P = 0.054). Finally, we did not find any association for A at least 3 and liver steatosis. Conclusion: PNPLA3 rs738409 polymorphism was associated with the severity of liver fibrosis in patients coinfected with HIV and hepatitis C virus, suggesting that this polymorphism might also play a significant role in the progression of hepatic fibrosis in this group of patients.This work has been supported by grants given by Fondo de Investigación de Sanidad en España (FIS) (Spanish Health Founds for Research) (grant numbers PI11/01556, PI14/01094, PI11/00245, PI14CIII/00011), and ‘Fundación para la Investigación y la Prevención del Sida en España’ (FIPSE) (grant number 361020/10). This work has been (partially) funded by the RD12/0017/0024 and RD12/0017/0004 projects as part of the Plan Nacional R+D+I and cofinanced by ISCIII – Subdirección General de Evaluación y el Fondo Europeo de Desarrollo Regional (FEDER). ‘Instituto de Salud Carlos III’ (grant numbers CD12/00442, CD13/00013 and RD12/0017/0024, respectively). This work has been (partially) funded by the RD12/0017 project as part of the Plan Nacional R+D+I and cofinanced by ISCIII – Subdirección General de Evaluación y el Fondo Europeo de Desarrollo Regional (FEDER).S

Ética de la investigación en ciencias sociales. El problematorio de ética, un recurso pedagógico para los dilemas de la investigación contemporánea

Depto. de Antropología Social y Psicología SocialFac. de Ciencias Políticas y SociologíaFALSEsubmitte

Técnica Mineral S.A. de C.V.

Se presenta el Proyecto de Aplicación Profesional en el que se trabajó en la exportación de los productos AFLABALAN y QUITAFLAX de la empresa jalisciense Técnica Mineral S.A. de C.V. a los mercados internos de El Salvador, Costa Rica, Perú, Colombia, Chile y Brasil. Estos mercados fueron elegidos en un principio por las ventajas geográficas que ofrecen como clientes potenciales para el productor mexicano, además de las ventajas que representa el trabajar con países con los que se comparten grandes similitudes como el idioma y ciertas raíces culturales que agilizan mucho la comunicación y, por lo tanto, la operación internacional. Conforme avanzó la investigación se fueron validando los objetivos en varios niveles de cada uno de los productos, como el mercado, costo de transporte, regulaciones específicas de cada país, etcétera. Esto nos dio como resultado información con mucha más fidelidad acerca de cuál es el país con las condiciones más aptas para abrir un nuevo mercado. Alprocesar esta información logramos ofrecer a la empresa las herramientas necesarias para la toma de decisiones acerca de la operación de exportación específica, cubriendo factores como cuánto exportar, a dónde exportar y cómo hacerlo

Carcinoma papilar en quiste de conducto tirogloso, diagnóstico por punción con aguja fina (paf)

El quiste tirogloso, es la anomalía congénita más frecuente en la región cervical, el cual puede presentar un componente maligno en menos del 1% de los casos. Se presenta una paciente femenina 31 años, con una masa palpable en la cara anterior con línea media del cuello y clínica e imagenologia compatible con quiste tirogloso, a quien se le realiza estudio citológico de material obtenido por punción con aguja fina, resultando categorización diagnostica de presuntivo para cáncer compatible con carcinoma papilar. La paciente fue sometida a extracción quirúrgica de la lesión, acompañada de tiroidectomía total. Se corroboró el diagnóstico de carcinoma papilar en el quiste tirogloso y además de microcarcinoma papilar en la glándula tiroides. En conclusión se recomienda la PAF en conjunto con la clínica e imagenologia como herramientas diagnósticas para el estudio de lesiones en la región cervical, útil además en lesiones quísticas. TitlePapillary Carcinoma in a Thyroglossal Duct Cyst diagnosed by Fine Needle AspirationAbstract Thyroglossal cysts, are the most frequent congenital anomaly in the cervical region, they present a malignant component in less than 1% of the cases. We present the case of a female patient 31 years old, presenting with a palpable mass in the anterior part of the neck. With a probable diagnosis of thyroglossal duct cyst papillary carcinoma. After fine needle aspiration and a probable diagnosis of Papillary carcinoma, the lesion was surgically removed and a total thyroidectomy was performed. Pathological analysis confirmed the presence of papillary carcinoma of the thyroglosal duct and microcarcinoma of the thyroid gland. In conclusion fine needle aspiration, clinical and imaging are good diagnostic tools for the study of cystic lesions

Genetic variation in CCR2 and CXCL12 genes impacts on CD4 restoration in patients initiating cART with advanced immunesupression.

OBJECTIVE:We investigated the association of genetic polymorphisms in chemokine and chemokine receptor genes with poor immunological recovery in HIV patients starting combined antiretroviral therapy (cART) with low CD4 T-cell counts. METHODS:A case-control study was conducted in 412 HIV-infected patients starting cART with CD4 T-cell count <200 cells/μL and successful viral control for two years. CD4 count increase below 200 cells/μL after two years on cART was used to define INR (immunological non-responder) patients. Polymorphisms in CXCL12, CCL5 and CCR2 genes were genotyped using sequenom's MassARRAY platform. RESULTS:Thirty two percent (134/412) of patients were classified as INR. After adjusting by age, route of HIV infection, length of infection before cART and viral hepatitis coinfection, CCR2 rs1799864-AG genotype was significantly associated with INR status (OR [95% CI]: 1.80 [1.04-3.11]; p = 0.04), and CXCL12 rs1801157-TT genotype showed a trend (OR [95% CI]: 2.47 [0.96-6.35]; p = 0.06). CONCLUSIONS:CCR2 rs1799864-AG or CXCL12 rs1801157-TT genotypes influence on the probability of poor CD4 recovery in the population of HIV patients starting cART with low CD4 counts. Genotyping of these polymorphisms could be used to estimate the risk of poor CD4 restoration, mainly in patients who are diagnosed late in the course of infection

Phenotype of Gambling Disorder Patients with Lotteries as a Preferred Form of Gambling

Lottery gambling can become an addictive behavior which can significantly interfere with daily functioning. The objectives of this work were to estimate the prevalence of lottery gambling, to assess the profile related to this gambling type in a large clinical sample of patients who met criteria for gambling disorder (GD), and to compare this profile with the other two non-strategic forms of gambling (slot-machines and bingo). Sample included n = 3,531 patients consecutively attended for treatment-seeking due to gambling-related problems. All the participants met criteria for GD and were into the range of 18 to 85 years old. Sociodemographic variables, GD severity, psychopathological state, and personality traits were assessed. Statistical comparisons between the groups defined by the patients’ gambling preference (lotteries versus other gambling activities) were conducted, with chi-square test and analysis of variance. The prevalence of lotteries as the only gambling activity was 2.5%, 8.9% for lottery gambling as primary activity with other secondary gambling types, and 20.6% for lotteries as primary or secondary gambling activity. Lottery gambling and bingo gambling were more prevalent among women (bingo included the highest percentage of women). Compared to slot machine gambling, lotteries and bingo grouped older patients and those with later age of onset of the gambling-related problems. Bingo gambling showed the highest psychological distress and the most dysfunctional personality traits. This study shows the high frequency of lottery gambling among treatment-seeking for GD patients, and it provides empirical evidence about the profile associated with this gambling activity compared to other non-strategic gambling forms. The likelihood of lottery gambling is higher for women, patients married or living with a stable partner, and those within higher social position indexes

Detection of early seeding of Richter transformation in chronic lymphocytic leukemia

Richter transformation (RT) is a paradigmatic evolution of chronic lymphocytic leukemia (CLL) into a very aggressive large B cell lymphoma conferring a dismal prognosis. The mechanisms driving RT remain largely unknown. We characterized the whole genome, epigenome and transcriptome, combined with single-cell DNA/RNA-sequencing analyses and functional experiments, of 19 cases of CLL developing RT. Studying 54 longitudinal samples covering up to 19 years of disease course, we uncovered minute subclones carrying genomic, immunogenetic and transcriptomic features of RT cells already at CLL diagnosis, which were dormant for up to 19 years before transformation. We also identified new driver alterations, discovered a new mutational signature (SBS-RT), recognized an oxidative phosphorylation (OXPHOS)(high)-B cell receptor (BCR)(low)-signaling transcriptional axis in RT and showed that OXPHOS inhibition reduces the proliferation of RT cells. These findings demonstrate the early seeding of subclones driving advanced stages of cancer evolution and uncover potential therapeutic targets for RT.Single-cell genomic and transcriptomic analyses of longitudinal samples of patients with Richter syndrome reveal the presence and dynamics of clones driving transformation from chronic lymphocytic leukemia years before clinical manifestatio

Discovering HIV related information by means of association rules and machine learning

Acquired immunodeficiency syndrome (AIDS) is still one of the main health problems worldwide. It is therefore essential to keep making progress in improving the prognosis and quality of life of affected patients. One way to advance along this pathway is to uncover connections between other disorders associated with HIV/AIDS-so that they can be anticipated and possibly mitigated. We propose to achieve this by using Association Rules (ARs). They allow us to represent the dependencies between a number of diseases and other specific diseases. However, classical techniques systematically generate every AR meeting some minimal conditions on data frequency, hence generating a vast amount of uninteresting ARs, which need to be filtered out. The lack of manually annotated ARs has favored unsupervised filtering, even though they produce limited results. In this paper, we propose a semi-supervised system, able to identify relevant ARs among HIV-related diseases with a minimal amount of annotated training data. Our system has been able to extract a good number of relationships between HIV-related diseases that have been previously detected in the literature but are scattered and are often little known. Furthermore, a number of plausible new relationships have shown up which deserve further investigation by qualified medical experts