Circulating microRNAs in sera correlate with soluble biomarkers of immune activation but do not predict mortality in ART treated individuals with HIV-1 infection: A case control study

Introduction: The use of anti-retroviral therapy (ART) has dramatically reduced HIV-1 associated morbidity and mortality. However, HIV-1 infected individuals have increased rates of morbidity and mortality compared to the non-HIV-1 infected population and this appears to be related to end-organ diseases collectively referred to as Serious Non-AIDS Events (SNAEs). Circulating miRNAs are reported as promising biomarkers for a number of human disease conditions including those that constitute SNAEs. Our study sought to investigate the potential of selected miRNAs in predicting mortality in HIV-1 infected ART treated individuals. Materials and Methods: A set of miRNAs was chosen based on published associations with human disease conditions that constitute SNAEs. This case: control study compared 126 cases (individuals who died whilst on therapy), and 247 matched controls (individuals who remained alive). Cases and controls were ART treated participants of two pivotal HIV-1 trials. The relative abundance of each miRNA in serum was measured, by RTqPCR. Associations with mortality (all-cause, cardiovascular and malignancy) were assessed by logistic regression analysis. Correlations between miRNAs and CD4+ T cell count, hs-CRP, IL-6 and D-dimer were also assessed. Results: None of the selected miRNAs was associated with all-cause, cardiovascular or malignancy mortality. The levels of three miRNAs (miRs -21, -122 and -200a) correlated with IL-6 while miR-21 also correlated with D-dimer. Additionally, the abundance of miRs -31, -150 and -223, correlated with baseline CD4+ T cell count while the same three miRNAs plus miR- 145 correlated with nadir CD4+ T cell count. Discussion: No associations with mortality were found with any circulating miRNA studied. These results cast doubt onto the effectiveness of circulating miRNA as early predictors of mortality or the major underlying diseases that contribute to mortality in participants treated for HIV-1 infection

Development and Validation of a Risk Score for Chronic Kidney Disease in HIV Infection Using Prospective Cohort Data from the D:A:D Study

Ristola M. on työryhmien DAD Study Grp ; Royal Free Hosp Clin Cohort ; INSIGHT Study Grp ; SMART Study Grp ; ESPRIT Study Grp jäsen.Background Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice. Methods and Findings A total of 17,954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with >= 3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR > 60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFR In the D:A:D study, 641 individuals developed CKD during 103,185 person-years of follow-up (PYFU; incidence 6.2/1,000 PYFU, 95% CI 5.7-6.7; median follow-up 6.1 y, range 0.3-9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was -2 (interquartile range -4 to 2). There was a 1: 393 chance of developing CKD in the next 5 y in the low risk group (risk score = 5, 505 events), respectively. Number needed to harm (NNTH) at 5 y when starting unboosted atazanavir or lopinavir/ritonavir among those with a low risk score was 1,702 (95% CI 1,166-3,367); NNTH was 202 (95% CI 159-278) and 21 (95% CI 19-23), respectively, for those with a medium and high risk score. NNTH was 739 (95% CI 506-1462), 88 (95% CI 69-121), and 9 (95% CI 8-10) for those with a low, medium, and high risk score, respectively, starting tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor. The Royal Free Hospital Clinic Cohort included 2,548 individuals, of whom 94 individuals developed CKD (3.7%) during 18,376 PYFU (median follow-up 7.4 y, range 0.3-12.7 y). Of 2,013 individuals included from the SMART/ESPRIT control arms, 32 individuals developed CKD (1.6%) during 8,452 PYFU (median follow-up 4.1 y, range 0.6-8.1 y). External validation showed that the risk score predicted well in these cohorts. Limitations of this study included limited data on race and no information on proteinuria. Conclusions Both traditional and HIV-related risk factors were predictive of CKD. These factors were used to develop a risk score for CKD in HIV infection, externally validated, that has direct clinical relevance for patients and clinicians to weigh the benefits of certain antiretrovirals against the risk of CKD and to identify those at greatest risk of CKD.Peer reviewe

Espreme que sai sangue: sensacionalismo nas fotografias dos jornais online Repórter Parintins e Gazeta Parintins

O presente trabalho têm como objetivo geral estudar o sensacionalismo nas fotografias dos jornais de Parintins com base na Análise do discurso. Para a realização da pesquisa, o artigo científico terá como marco teórico, Orlandi (2002) e Mainguenau (2013) com enfoque o Discurso. Para a realização da pesquisa, o artigo científico terá como marco teórico, (autores) com enfoque o Fotojornalismo e conceitos de Sensacionalismo será abordado com a concepção dos autores Hernandes (2006) e Amaral (2005). O nosso material de coleta serão as fotografias dos jornais Repórter Parintins e Gazeta Parintins que noticiam tragédias de modo que usam o sensacionalismo para causar maior repercussão à população. Desta forma iremos buscar compreender como o fotojornalismo é usado nos jornais, quais são os critérios para as fotografias circularem nos veículos de comunicação e identificar as sensações causadas nas pessoas através das fotografias das matérias do jornal. O tema foi escolhido pela influência que o jornal aplica sobre a população nas matérias informativas publicadas em seu endereço na internet. Deste modo, por meio das redes sociais, o retorno para empresa de comunicação a respeito do posicionamento da polução é mais rápido devido à interatividade apontada por Recuero (2009). Com isso a temática foi escolhida pela grande repercussão que causa na população parintinense. Os jornais Repórter Parintins e Gazeta Parintins se dá como objeto de estudo por ser jornais mais veiculado entre a população do município de Parintins O tema se faz relevante pois possibilitará a população de modo geral a identificar o sensacionalismo usados no fotojornalismo que as empresas de comunicação utilizam para vender mais o jornal. No campo metodológico, o artigo se constitui por ser do tipo de pesquisa explicativa, descritiva, com uma abordagem qualitativa.Palavras-Chaves: Fotojornalismo; Sensacionalismo; Análise do Discurso; Repórter Parintins; Gazeta Parintins

Estimation of the pKa values of water ligands in transition metal complexes using density functional theory with polarized continuum model solvent corrections

The deprotonation energies of the water ligands in a set of 40 d-block metal complexes have been calculated using density functional theory with polarized continuum model solvent corrections. The complexes include 13 aqua ions [M(OH2)n]2+/3+ and a variety of aqua complexes with organic co-ligands, whose experimental pKa values have been reported in the literature. For comparison, the deprotonation energies of a set of 60 organic and inorganic molecules with experimental pKa values ranging from -25 (HSbF6) to +52 (C2H6) have also been calculated. Three different classes of acids are identified as giving different slopes in plots of pKaversus deprotonation energies; namely non-hydroxy acids, hydroxy acids, and the metal complexes. The correlation coefficients for the straight lines obtained for these three classes are 0.96, 0.97 and 0.92 respectively. Better correlations are found for sub-sets of the complexes, such as the 31 first row complexes (correlation coefficient 0.95).For several of the complexes, comparison of the calculated and observed pKa values, together with changes in the geometry upon optimization, offer new insights into the possible solution structures. It is concluded that DFT calculations incorporating solvent corrections can be used to give reasonable estimates of pKa values for the aqua ligands in a range of complex types

Risk for opportunistic disease and death after reinitiating continuous antiretroviral therapy in patients with HIV previously receiving episodic therapy: a randomized trial.

Collaboratore per la suddetta ricerca multicentrica in quanto membro di SMART Study Grou

Interruption of antiretroviral therapy is associated with increased plasma cystatin C.

Collaboratore della suddetta ricerca in quanto membro del INSIGHT SMART Study Grou

Viral resuppression and detection of drug resistance following interruption of a suppressive non-nucleoside reverse transcriptase inhibitor-based regimen.

Collaboratore per la suddetta ricerca multicentrica in quanto membro di SMART Study Group

Inferior clinical outcome of the CD4+ cell count-guided antiretroviral treatment interruption strategy in the SMART study: role of CD4+ Cell counts and HIV RNA levels during follow-up.

Collaboratore per la suddetta ricerca in quanto membro di SMART Study Grou