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

Archeometric study of the more ancient painted wall found in Sicily (Apaforte – Licata)

In the present work, an analytical study of painted plaster samples coming from an ancient crypt, dated back to 4th – 3rd cent B.C. and located in Licata (Sicily, Southern Italy), has been carried out. This crypt situated in the street called “c.daApaforte” is an interesting hypogeum composed of a single room made of stone blocks. The importance of this crypt is represented by the presence of the most ancient painted wall recovered in Sicilian hypogea structures. In order to identify the pigmenting agents, the preparation layers and the deterioration processeswe carried out non-destructive micro-Raman spectroscopy and micro-destructive analyses through SEM-EDS. Preliminary characterization of samples was done by optical microscopy (OM). The micro-Raman measurements have been performed in order to investigate the molecular nature of the used materials and obtain a preliminary characterization of the decorated surfaces. The quantitative analysis of the chemical composition of the different layers (pigments, preparation layers, deteriorated parts) has been obtained by SEM-EDS. Finally, preliminary macroscopic and thin section analysis have been carried out with the aim at characterizing plaster features and degradation processes. In order to establish the production technique used by the craftsmen, the results were compared with our recent data on Hellenistic plasters coming from an ancient buildings located in Licata and dated back 2ndcent B.C (Aquilia E. et al., 2012)

Archeometric investigation on wall paintings from the most ancient Hellenistic hypogeum found in Sicily (C.da Apaforte-Licata (AG))s

In the present work, an analytical study of paintings from an ancient hypogeum, dated back to 4th–3rd cent B.C. and located in Licata (Sicily, Southern Italy) has been carried out. A selection of representative red, yellow and white wall colored plasters have been sampled and analyzed in non-destructive and micro-destructive way to identify the pigmenting agents, preparation layers and study the deterioration processes. In particular, the quantitative analysis of the chemical composition of the different layers (pigments, preparation layers, deteriorated parts) has been obtained through scanning electron microscopy coupled with energy-dispersive spectrometry (SEM–EDS), while micro-Raman spectroscopy have been performed to investigate the molecular nature of the coloring agents used in the pigment layer. Finally, preliminary macroscopic and thin section analyses (OM) have been carried out with the aim to characterize plaster features and degradation processes. The obtained results, together with previous data on Hellenistic art in Sicily, may be helpful to create a database about the evolution of mural painting in Sicily as well as identify raw materials, pigment agents and painting techniques used in local plasters manufacture

Archeometric investigation on wall paintings from the most ancient Hellenistic hypogeum found in Sicily (C.da Apaforte-Licata (AG))

In the present work, an analytical study of paintings from an ancient hypogeum, dated back to 4th–3rd cent B.C. and located in Licata (Sicily, Southern Italy) has been carried out. A selection of representative red, yellow and white wall colored plasters have been sampled and analyzed in non-destructive and micro-destructive way to identify the pigmenting agents, preparation layers and study the deterioration processes. In particular, the quantitative analysis of the chemical composition of the different layers (pigments, preparation layers, deteriorated parts) has been obtained through scanning electron microscopy coupled with energy-dispersive spectrometry (SEM–EDS), while micro-Raman spectroscopy have been performed to investigate the molecular nature of the coloring agents used in the pigment layer. Finally, preliminary macroscopic and thin section analyses (OM) have been carried out with the aim to characterize plaster features and degradation processes. The obtained results, together with previous data on Hellenistic art in Sicily, may be helpful to create a database about the evolution of mural painting in Sicily as well as identify raw materials, pigment agents and painting techniques used in local plasters manufacture

Diagnosis and conservation by using portable equipment: the case of St. Maria Cathedral in Randazzo (Sicily)

The diagnosis of historical building materials is quite relevant for a complete knowledge of construction rules as well as during focused restoration actions. In particular, the identification of natural building stones employed in the manufacture of historical monuments is the first step to understand causes of weathering processes, to choose the most appropriate conservation and/or protection treatments and to select the materials to employ in replacements during the restoration works. In some cases, the high architectural value of the investigated elements prevents any sampling, needing the application of portable instruments for the non-destructive in situ analysis of building stone materials. However, the routinely application of portable methodologies to diagnosis and conservation actions imply the standardization of testing procedures and creation of appropriate reference database to carry out reliable comparisons between building and (probable) quarry materials. For the aforementioned, in this contribute we present an experimental study performed by using a portable X-ray device, namely the Bruker Tracer IV instrument on reference basalt natural stones sampled in some of the Sicilian quarries and used in the local historical architecture to standardize and subsequently for in situ analysis of building materials. Thus, non-destructive measurements have been carried out on the basalt columns of the St. Mary Cathedral in Randazzo (Sicily) - a relevant historical building founded in the 12th century, but completely renovated during the Renaissance period (Cultrone et a., 2001; Sanfilippo, 2008) - in order to test the method for stone classification and identification of quarries. This approach has allowed to identify raw materials employed in the manufacture of the columns of the Cathedral, supporting the creation of a database of Etna lavas quarried over the time for building manufacture and the standardization of the instrument for future in situ applications