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Find video protocols related to scientific articles indexed in Pubmed.
A very low geno2pheno false positive rate is associated with poor viro-immunological response in drug-naïve patients starting a first-line HAART.
PLoS ONE
PUBLISHED: 08-25-2014
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We previously found that a very low geno2pheno false positive rate (FPR ? 2%) defines a viral population associated with low CD4 cell count and the highest amount of X4-quasispecies. In this study, we aimed at evaluating whether FPR ? 2% might impact on the viro-immunological response in HIV-1 infected patients starting a first-line HAART.
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Reliability and clinical relevance of the HIV-1 drug resistance test in patients with low viremia levels.
Clin. Infect. Dis.
PUBLISHED: 01-14-2014
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We evaluated reliability and clinical usefulness of genotypic resistance testing (GRT) in patients for whom combination antiretroviral therapy (cART) was unsuccessful with viremia levels 50-1000 copies/mL, for whom GRT is generally not recommended by current guidelines.
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Circulation of HIV-1 CRF02_AG among MSM Population in Central Italy: A Molecular Epidemiology-Based Study.
Biomed Res Int
PUBLISHED: 08-10-2013
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Introduction. The evolutionary and demographic history of the circular recombinant form CRF02_AG in a selected retrospective group of HIV-1 infected men who have sex with men (MSM) resident in Central Italy was investigated. Methods. A total of 55 HIV-1 subtype CRF02_AG pol sequences were analyzed using Bayesian methods and a relaxed molecular clock to reconstruct their dated phylogeny and estimate population dynamics. Results. Dated phylogeny indicated that the HIV-1 CRF02_AG strains currently circulating in Central Italy originated in the early 90s. Bayesian phylogenetic analysis revealed the existence of a main HIV-1 CRF02_AG clade, introduced in the area of Rome before 2000 and subsequently differentiated in two different subclades with a different date of introduction (2000 versus 2005). All the sequences within clusters were interspersed, indicating that the MSM analyzed form a close and restricted network where the individuals, also moving within different clinical centers, attend the same places to meet and exchange sex. Conclusions. It was suggested that the HIV-1 CRF02_AG epidemic entered central Italy in the early 1990s, with a similar trend observed in western Europe.
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Structural modifications induced by specific HIV-1 protease-compensatory mutations have an impact on the virological response to a first-line lopinavir/ritonavir-containing regimen.
J. Antimicrob. Chemother.
PUBLISHED: 05-17-2013
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This study evaluates the impact of specific HIV-1 protease-compensatory mutations (wild-type amino acids in non-B subtypes) on virological response to a first-line lopinavir/ritonavir-containing regimen in an HIV-1 subtype B-infected population.
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The genotypic false positive rate determined by V3 population sequencing can predict the burden of HIV-1 CXCR4-using species detected by pyrosequencing.
PLoS ONE
PUBLISHED: 01-14-2013
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The false-positive rate (FPR) is a percentage-score provided by Geno2Pheno-algorithm indicating the likelihood that a V3-sequence is falsely predicted as CXCR4-using. We evaluated the correlation between FPR obtained by V3 population-sequencing and the burden of CXCR4-using variants detected by V3 ultra-deep sequencing (UDPS) and Enhanced-Sensitivity Trofile assay (ESTA).
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HIV-1 Genetic Variability and Clinical Implications.
ISRN Microbiol
PUBLISHED: 01-01-2013
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Despite advances in antiretroviral therapy that have revolutionized HIV disease management, effective control of the HIV infection pandemic remains elusive. Beyond the classic non-B endemic areas, HIV-1 non-B subtype infections are sharply increasing in previous subtype B homogeneous areas such as Europe and North America. As already known, several studies have shown that, among non-B subtypes, subtypes C and D were found to be more aggressive in terms of disease progression. Luckily, the response to antiretrovirals against HIV-1 seems to be similar among different subtypes, but these results are mainly based on small or poorly designed studies. On the other hand, differences in rates of acquisition of resistance among non-B subtypes are already being observed. This different propensity, beyond the type of treatment regimens used, as well as access to viral load testing in non-B endemic areas seems to be due to HIV-1 clade specific peculiarities. Indeed, some non-B subtypes are proved to be more prone to develop resistance compared to B subtype. This phenomenon can be related to the presence of subtype-specific polymorphisms, different codon usage, and/or subtype-specific RNA templates. This review aims to provide a complete picture of HIV-1 genetic diversity and its implications for HIV-1 disease spread, effectiveness of therapies, and drug resistance development.
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Genetic diversity of HIV type 1 in Montenegro.
AIDS Res. Hum. Retroviruses
PUBLISHED: 12-29-2011
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Human immunodeficiency virus type 1 (HIV-1) is characterized by high genetic variability due to its high replication rate and the lack of proofreading activity of the reverse transcriptase enzyme. On the basis of phylogenetic analysis performed on numerous isolates from all over the world, HIV-1 is subdivided into types, subtypes, subsubtypes, circulating recombinant forms, and unique recombinant forms. No data are currently available about the circulation of HIV-1 types in Montenegro. Here, we describe the genetic variability of HIV-1 strains identified in plasma samples of patients from Montenegro. Phylogenetic analysis on 32 HIV-1 sequences was carried out. The prevalent circulating HIV-1 subtype is B. The strains were interspersed within the tree. Two main clades (I and II) may suggest independent introductions of HIV-1 subtype B into Montenegro, although other epidemiological evidence will be needed to assume a small number of introductions. No obvious evidence of clustering by residence, age, or sex was found (data not shown). Nelfinavir resistance was found, though lopinavir is the only PI administered. Continuous monitoring of HIV-1-infected individuals is crucial to a better understand of the epidemiology of the B subtype in Montenegro.
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Lifestyle modifications after acute coronary syndromes in a subset of the AMI-Florence 2 Registry.
Acta Cardiol
PUBLISHED: 10-17-2011
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The aim of this study was to evaluate the adherence to recommendations for secondary prevention of cardiovascular diseases in patients with acute coronary syndromes (ACS).
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Sentinel mutations in standard population sequencing can predict the presence of HIV-1 reverse transcriptase major mutations detectable only by ultra-deep pyrosequencing.
J. Antimicrob. Chemother.
PUBLISHED: 09-02-2011
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This proof-of-concept study aimed to identify whether mutations considered not yet relevant for drug resistance (but located at key drug-resistance positions) can act as sentinels of minority resistant variants in HIV-1 drug-naive patients.
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Drug resistance among drug-naive and first-line antiretroviral treatment-failing children in Cameroon.
Pediatr. Infect. Dis. J.
PUBLISHED: 08-06-2011
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Scale-up to antiretroviral therapy (ART) requires surveillance for HIV drug resistance. With the goal of attaining 100% pediatric ART coverage in Cameroon, strategies to limit the spread of HIV resistance among children are very important.
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Docking analysis and resistance evaluation of clinically relevant mutations associated with the HIV-1 non-nucleoside reverse transcriptase inhibitors nevirapine, efavirenz and etravirine.
ChemMedChem
PUBLISHED: 07-25-2011
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An integrated computational and statistical approach was used to determine the association of non-nucleoside reverse transcriptase inhibitors (NNRTIs) nevirapine, efavirenz and etravirine with resistance mutations that cause therapeutic failure and their impact on NNRTI resistance. Mutations detected for nevirapine virological failure with a prevalence greater than 10% in the used patient set were: K103N, Y181C, G190A, and K101E. A support vector regression model, based on matched genotypic/phenotypic data (n=850), showed that among 6365 analyzed mutations, K103N, Y181C and G190A have the first, third, and sixth greatest significance for nevirapine resistance, respectively. The most common indicator of treatment failure for efavirenz was K103N mutation present in 56.7% of the patients where the drug failed, followed by V108I, L100I, and G190A. For efavirenz resistance, K103N, G190, and L100I have the first, fourth, and eighth greatest significance, respectively, as determined in support vector regression model. No positive interactions were observed among nevirapine resistance mutations, while a more complex situation was observed with treatment failure of efavirenz and etravirine, characterized by the accumulation of multiple mutations. Docking simulations and free energy analysis based on docking scores of mutated human immunodeficiency virus (HIV) RT complexes were used to evaluate the influence of selected mutations on drug recognition. Results from support vector regression were confirmed by docking analysis. In particular, for nevirapine and efavirenz, a single mutation K103N was associated with the most unfavorable energetic profile compared to the wild-type sequence. This is in line with recent clinical data reporting that diarylpyrimidine etravirine, a very potent third generation drug effective against a wide range of drug-resistant HIV-1 variants, shows increased affinity towards K103N/S mutants due to its high conformational flexibility.
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Interpretation of genotypic HIV-1 resistance to darunavir and virological response: validation of available systems and of a new score.
Antivir. Ther. (Lond.)
PUBLISHED: 06-21-2011
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There is not yet consensus on interpretation of genotypic HIV-1 resistance to darunavir (DRV). We validated existing rules and a newly derived score.
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Metabolic profile of amniotic fluid as a biochemical tool to screen for inborn errors of metabolism and fetal anomalies.
Mol. Cell. Biochem.
PUBLISHED: 05-19-2011
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Physiologic concentration in amniotic fluid (AF) of several metabolites has not been established with certainty. In this study, we initially assayed purines, pyrimidines, and amino compounds in 1,257 AF withdrawn between the 15th and the 20th week of gestation from actually normal pregnancies (normal gestations, normal offspring). Results allowed to determine physiologic reference intervals for 45 compounds. In these AF, not all purines and pyrimidines were detectable and uric acid (238.35±76.31 ?mol/l) had the highest concentration. All amino compounds were measurable, with alanine having the highest concentration (401.10±88.47 ?mol/l). In the second part of the study, we performed a blind metabolic screening of AF to evaluate the utility of this biochemical analysis as an additional test in amniocenteses. In 1,295 additional AF from normal pregnancies, all metabolites fell within the confidence intervals determined in the first part of the study. In 24 additional AF from women carrying Downs syndrome-affected fetuses, glutamate, glutamine, glycine, taurine, valine, isoleucine, leucine, ornithine, and lysine were different from physiologic reference values. One AF sample showed phenylalanine level of 375.54 ?mol/l (mean value in normal AF=65.07 ?mol/l) and was from a woman with unreported phenylketonuria with mild hyperphenylalaninemia (serum phenylalanine=360.88 ?mol/l), carrying the IVS 4+5 G-T and D394A mutations. The fetus was heterozygote for the maternal D394A mutation. An appropriate diet maintained the mother phenylalanine in the range of normality during pregnancy, avoiding serious damage in fetal and neonatal development. These results suggest that the metabolic screening of AF might be considered as an additional biochemical test in amniocenteses useful to highlight anomalies potentially related to IEM.
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Molecular epidemiology of HIV type 1 CRF02_AG in Cameroon and African patients living in Italy.
AIDS Res. Hum. Retroviruses
PUBLISHED: 05-06-2011
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HIV-1 CRF02_AG accounts for >50% of infected individuals in Cameroon. CRF02_AG prevalence has been increasing both in Africa and Europe, particularly in Italy because of migrations from the sub-Saharan region. This study investigated the molecular epidemiology of CRF02_AG in Cameroon by employing Bayesian phylodynamics and analyzed the relationship between HIV-1 CRF02_AG isolates circulating in Italy and those prevalent in Africa to understand the link between the two epidemics. Among 291 Cameroonian reverse transcriptase sequences analyzed, about 70% clustered within three distinct clades, two of which shared a most recent common ancestor, all related to sequences from Western Africa. The major Cameroonian clades emerged during the mid-1970s and slowly spread during the next 30 years. Little or no geographic structure was detected within these clades. One of the major driving forces of the epidemic was likely the high accessibility between locations in Southern Cameroon contributing to the mobility of the population. The remaining Cameroonian sequences and the new strains isolated from Italian patients were interspersed mainly within West and Central African sequences in the tree, indicating a continuous exchange of CRF02_AG viral strains between Cameroon and other African countries, as well as multiple independent introductions in the Italian population. The evaluation of the spread of CRF02_AG may provide significant insight about the future dynamics of the Italian and European epidemic.
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Improving the prediction of virological response to tipranavir: the development and validation of a tipranavir-weighted mutation score.
Antivir. Ther. (Lond.)
PUBLISHED: 11-03-2010
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The purpose of this study was to develop a tipranavir-weighted mutation score that provides guidance to treating physicians on the relative effect of specific protease mutations on tipranavir activity.
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Different evolution of genotypic resistance profiles to emtricitabine versus lamivudine in tenofovir-containing regimens.
J. Acquir. Immune Defic. Syndr.
PUBLISHED: 08-27-2010
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To investigate genotypic resistance profiles to emtricitabine + tenofovir (FTC + TDF) in-vivo and in-vitro, and compare them with lamivudine + tenofovir (3TC + TDF).
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Population dynamics of HIV-1 subtype B in a cohort of men-having-sex-with-men in Rome, Italy.
J. Acquir. Immune Defic. Syndr.
PUBLISHED: 08-13-2010
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A recent increase in HIV diagnoses among men-having-sex-with-men (MSM) has been shown by surveillance data from Europe and Italy, and new approaches to inferring viral population dynamics from heterochronously sampled gene sequences have been developed. The aim of this study was to reconstruct the epidemiological history of HIV-1 subtype B in a homogeneous group of Italian MSM using a coalescent-based Bayesian framework. A total of 125 HIV-1 subtype B pol sequences were analyzed using Bayesian methods and a relaxed molecular clock to reconstruct their dated phylogeny and estimate population dynamics. At least 10 epidemiological clusters of 3-9 isolates were identified: half including the largest clades originated in the early 1990s and the other half radiated from 1999. Demographic analysis showed that the HIV epidemic grew in accordance with a logistic model characterized by a rapid exponential increase in the effective number of infections (r = 1.54 year) starting from the early 1980s and reaching a plateau 10 years later. Our data suggest that the HIV B epidemic entered our MSM population through multiple transmission chains about 20 years later than in other Western European country. Epidemiological clusters originating in the early 2000s suggest a recent re-emergence of HIV in Italian MSM.
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Use of novel antiretroviral agents in rescue regimens: a case of early virological failure to raltegravir.
Scand. J. Infect. Dis.
PUBLISHED: 01-21-2010
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In patients with virological failure during highly active antiretroviral therapy (HAART) and drug resistance, guidelines recommend the achievement of maximal virological suppression by the use of a new regimen with at least 2 active drugs. We describe the clinical outcome of a heavily antiretroviral-experienced patient who experienced early failure to raltegravir.
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Determination of atropine enantiomers in ophthalmic solutions by liquid chromatography using a Chiral AGP column.
J AOAC Int
PUBLISHED: 02-09-2009
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Many therapeutic agents are commercialized under their racemic form. The enantiomers can show differences in the pharmacokinetic and pharmacodynamic profile. The use of a pure enantiomer in pharmaceutical formulations may result in a better therapeutic index and fewer adverse effects. Atropine, an alkaloid of Atropa belladonna, is a racemic mixture of l-hyoscyamine and d-hyoscyamine. It is widely used to dilate the pupil. To quantify these enantiomers in ophthalmic solutions, an HPLC method was developed and validated using a Chiral AGP column at 20 degrees C. The mobile phase consisted of a buffered phosphate solution (containing 10 mM 1-octanesulfonic acid sodium salt and 7.5 mM triethylamine, adjusted to pH 7.0 with orthophosphoric acid) and acetonitrile (99 + 1, v/v). The flow rate was 0.6 ml/min, with UV detection at 205 nm. In the concentration range of 14.0-26.0 microg/mL, the method was found to be linear (r > 0.9999), accurate (with recovery of 100.1-100.5%), and precise (RSD system < or = 0.6%; RSD intraday < or = 1.1%; RSD interday < or = 0.9%). The method was specific, and the standard and sample solutions were stable for up to 72 h. The factorial design assures robustness with a variation of +/- 10% in the mobile phase components and 2 degrees C of column temperature. The complete validation, including stress testing and factorial design, was studied and is presented in this research.
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Dynamics of NRTI resistance mutations during therapy interruption.
AIDS Res. Hum. Retroviruses
PUBLISHED: 02-03-2009
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Abstract To date, very little information is available regarding the evolution of drug resistance mutations during treatment interruption (TI). Using a survival analysis approach, we investigated the dynamics of mutations associated with resistance to nucleoside analogue reverse transcriptase inhibitors (NRTIs) during TI. Analyzing 132 patients having at least two consecutive genotypes, one at last NRTI-containing regimen failure, and at least one during TI, we observed that the NRTI resistance mutations disappear at different rates during TI and are lost independently of each other in the majority of patients. The disappearance of the K65R and M184I/V mutations occurred in the majority of patients, was rapid, and was associated with the reemergence of wild-type virus, thus showing their negative impact on viral fitness. Overall, it seems that the loss of NRTI drug resistance mutations during TI is not an ordered process, and in the majority of patients occurs without specific interaction among mutations.
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Frasier syndrome: four new cases with unusual presentations.
Arq Bras Endocrinol Metabol
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Frasier syndrome (FS) is characterized by gonadal dysgenesis and nephropathy. It is caused by specific mutations in the Wilms tumor suppressor gene (WT1) located in 11p23. Patients with the 46,XY karyotype present normal female genitalia with streak gonads, and have higher risk of gonadal tumor, mainly, gonadoblastoma. Therefore, elective bilateral gonadectomy is indicated. Nephropathy in FS consists in nephrotic syndrome (NS) with proteinuria that begins early in childhood and progressively increases with age, mainly due to nonspecific focal and segmental glomerular sclerosis (FSGS). Patients are generally unresponsive to steroid and immunosuppressive therapies, and will develop end-stage renal failure (ESRF) during the second or third decade of life. We report here four cases of FS diagnosis after identification of WT1 mutations. Case 1 was part of a large cohort of patients diagnosed with steroid-resistant nephrotic syndrome, in whom the screening for mutations within WT1 8-9 hotspot fragment identified the IVS9+5G>A mutation. Beside FS, this patient showed unusual characteristics, such as urinary malformation (horseshoe kidney), and bilateral dysgerminoma. Cases 2 and 3, also bearing the IVS9+5G>A mutation, and case 4, with IVS9+1G>A mutation, were studied due to FSGS and/or delayed puberty; additionally, patients 2 and 4 developed bilateral gonadal tumors. Since the great majority of FS patients have normal female external genitalia, sex reversal is not suspected before they present delayed puberty and/or primary amenorrhea. Therefore, molecular screening of WT1 gene is very important to confirm the FS diagnosis.
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HIV-1 non-B subtypes in Italy: a growing trend.
New Microbiol.
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Sequence analysis plays an important role in the management of patients chronically infected with HIV-1. Knowledge of the viral genotype and drug resistance mutations is crucial for the correct management of these patients. From this point of view, the experience of researchers in the HIV-1 field and the introduction of the HIV-1 genotyping resistance test has been fundamental. Several molecular tools are available to assist the provider in interpreting genotypic test results including phylogenetics. However, it should be remembered that antiretroviral drug designs, resistance studies and interpretation systems have been largely based on HIV-1 subtype B, which has been historically the most prevalent subtype in Western countries. Due to increased migration towards Europe, especially from Africa and South- East Asia, the molecular epidemiology of HIV-1 in Western Europe, including Italy, is changing. HIV-1 non-B subtypes have entered Europe and their prevalence has increased over the last years. In Italy, the estimated percentage of infection with non-B subtypes ranges from 2.4 % to 19.4%. However, the true prevalence of HIV-1 non-B subtypes in this country is still not well known and probably underestimated. This may have important clinical and diagnostic implications. A strict molecular epidemiological survey and a reinforced sequencing strategy are required.
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Should we improve the management of NSTEMI? Results from the population-based "acute myocardial infarction in Florence 2" (AMI-Florence 2) registry.
Intern Emerg Med
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ST-segment and non-ST-segment elevation myocardial infarction (STEMI, NSTEMI) have opposite epidemiology, the latter being nowadays more common than the former. Consistently with these epidemiological trends, application of evidence-based clinical practice guidelines on the management of NSTEMI should be promoted. We compared clinical features, hospital management and prognosis of STEMI/NSTEMI in an unselected cohort of 1,496 prospectively enrolled patients (STEMI, 36.9 % and NSTEMI, 63.1 %), admitted in 1 year to one of the six hospitals in Florence health district (Italy). Vital status was assessed after 1 year. NSTEMI patients were older, more often female, and affected by cardiovascular and non-cardiovascular comorbidities. Percutaneous coronary intervention (PCI) was performed more often in STEMI (82 %) than in NSTEMI patients (48 %, p < 0.001). Aspirin, clopidogrel, statins, beta-blockers, and ACE-inhibitors were prescribed more frequently in STEMI. In-hospital mortality was significantly lower in NSTEMI than in STEMI (4.2 vs. 8.9 %, p < 0.001), even after adjusting for confounders in a multivariable logistic model (OR 0.27, 95 % CI 0.16-0.45). One-year mortality was similar in NSTEMI and STEMI patients in an unadjusted comparison (18.0 vs. 16.7 %, p = 0.51), but it was lower in NSTEMI patients in multivariable Cox analysis (HR 0.56, 95 % CI 0.42-0.75). PCI reduced the risk of 1-year mortality similarly in STEMI (HR 0.47, 95 % CI 0.28-0.79) and NSTEMI (HR 0.41, 95 % CI 0.28-0.60). PCI reduces mortality in both STEMI and NSTEMI, but it is underutilised in patients with NSTEMI. To improve overall prognosis of AMI, efforts should be made at improving the care of NSTEMI patients.
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Cationic porphyrins are reversible proteasome inhibitors.
J. Am. Chem. Soc.
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The aim of this study is to verify if water-soluble porphyrins can be used as proteasome inhibitors. We have found that cationic porphyrins inhibit proteasome peptidase activities much more effectively than the corresponding anionic derivatives. The relevance of electrostatics in driving porphyin-proteasome interactions has been confirmed by the observation that the inhibitory efficiency of the cationic macrocycles decreases with the number of positive substituents. We have also investigated various metalloporphyrins, which differ due to the different propension of the central metal ion toward axial coordination. Our experimental results indicate that the naked cationic porphyrins are the most active in reversibly inhibiting the three main protease activities of the proteasome in the micromolar range. A spectroscopic characterization of porphyrin-proteasome interactions by UV-vis spectra parallels the results of inhibition assays: the higher the inhibitory effect the stronger the spectroscopic variations are. To interpret the action of porphyrins at a molecular level, we have performed calculations evidencing that cationic porphyrins may hinder the access to the canonical proteolytic site on the proteasome ?5 subunit. In particular, an inspection of the top-scoring docking modes shows that the tetracationic porphyrin blocks the catalytic pocket, close to the N termini of the ?5 proteasome subunit, more efficiently than its anionic counterpart. Proteasome inhibition activity of porphyrins unites their known anticancer properties making them suitable as a scaffold for the design of novel multitargeted molecules.
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Application of 2011 American College of Cardiology Foundation/American Society of Echocardiography appropriateness use criteria in hospitalized patients referred for transthoracic echocardiography in a community setting.
J Am Soc Echocardiogr
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A recent American College of Cardiology Foundation and American Society of Echocardiography document updated previous appropriate use criteria (AUC) for echocardiography. The aim of this study was to explore the application of the new AUC, and the resulting appropriateness rate, in hospitalized patients referred for transthoracic echocardiography (TTE) in a community setting.
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Copper(II) interaction with peptide fragments of histidine-proline-rich glycoprotein: Speciation, stability and binding details.
J. Inorg. Biochem.
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GHHPH is the peptide repeat present in histidine-proline rich glycoprotein (HPRG), a plasma glycoprotein involved in angiogenesis process. The copper(II) ions interaction with mono (Ac-GHHPHG-NH(2)) and its bis-repeat (Ac-GHHPHGHHPHG-NH(2)) was investigated by means of potentiometric and spectroscopic techniques. To single out the copper(II) coordination environments of different species formed with Ac-GHHPHG-NH(2), three single point mutated peptides were also synthesized and their ability to coordinate Cu(2+) investigated. Ac-GHHPHG-NH(2) binds Cu(2+) by the imidazole side chain and the amide nitrogen deprotonation that takes place towards the N-terminus. The bis-repeat is able to bind Cu(2+) more efficiently than Ac-GHHPHG-NH(2). This difference is not only due to the number of His residues in the sequence but also to the different binding sites. In fact, the comparison of the potentiometric and spectroscopic data of the copper(II) complexes with a bis-repeatPeg construct Ac-(GHHPHG)-Peg-(GHHPHG)-NH(2) and those of the metal complexes with Ac-HGHH-NH(2), indicates that the central HGHH amino acid sequence is the main copper(II) binding site.
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Characterization of drug resistance mutations in naïve and ART-treated patients infected with HIV-1 in Yaounde, Cameroon.
J. Med. Virol.
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Currently the prevalence of HIV-1 infection in Cameroon is 5.1%, CRF02_AG subtype is responsible for about 50% of infections. Since an HIV-1 drug resistance test is not yet available widely, accurate data on the prevalence of resistant viral strains are missing. The objective of this study was to determine HIV-1 genetic diversity and to characterize HIV-1 mutations conferring drug resistance among antiretroviral therapy (ART)-naïve and ART-treated patients. A cohort of 239 patients infected with HIV were followed-up between January 2007 and July 2010 in Cameroon. Two hundred and sixteen plasma samples were sequenced for phylogenetic analysis and identification of drug resistance mutations in the HIV-1 pol region. A significant genetic diversity was found: Seven pure subtypes (A1, A3, D, F1, F2, G, H), nine circulating recombinant forms (CRFs: 01_AE, 02_AG, 06cpx, 09cpx, 11cpx, 13cpx, 16cpx, 18cpx, 37cpx) and one new unique recombinant form (URF) (G/F2). The rate of transmitted drug resistance (TDR) in naïve patients was 8.2% (4/49). Around 80% of patients failing a first-line ART harbored a virus with at least one resistance mutation to two antiretroviral (ARV) classes, and 36% of those failing a second-line regimen carried a virus with at least one resistant mutation to three ARV classes. The high level of drug resistance observed in the cohort is alarming because this occurred as a result of only few years of treatment. Adherence to therapy, adequate education of physicians, and the appropriate use of genotypic resistance assay are critical points of intervention for the improvement of patient care.
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Comparative analysis of drug resistance among B and the most prevalent non-B HIV type 1 subtypes (C, F, and CRF02_AG) in Italy.
AIDS Res. Hum. Retroviruses
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In recent years, increasing numbers of patients infected with HIV-1 non-B subtypes have been treated with modern antiretroviral regimens. Therefore, a better knowledge of HIV drug resistance in non-B strains is crucial. Thus, we compared the mutational pathways involved in drug resistance among the most common non-B subtypes in Italy (F, C, and CRF02_AG) and the B subtype. In total, 2234 pol sequences from 1231 virologically failing patients from Central Italy were analyzed. The prevalence of resistance mutations in protease and reverse transcriptase between non-B and B subtypes has been evaluated. Among patients treated with nucleoside/nucleotide reverse transcriptase inhibitors (NRTI) and with thymidine analogues (TA) experience, TAMs1 M41L and L210W were less prevalent in CRF02_AG, while TAMs2 T215F and K219E were more prevalent in the F subtype. In NRTI-treated patients having experience with abacavir, didanosine, tenofovir, or stavudine the K65R mutation was mostly prevalent in the C subtype. In non-NRTI (NNRTI)-treated patients infected by the C subtype the prevalence of K103N was lower than in patients infected with other subtypes, while the prevalence of Y181C and Y188L was higher compared to subtype B. The prevalence of Y181C was higher also in subtype F as compared to subtype B. In patients treated with protease inhibitors, L89V was predominantly found in CRF02_AG, while the TPV resistance mutation T74P was predominantly found in the C subtype. Some differences in the genotypic drug resistance have been found among patients infected with B, C, F, and CRF02_AG subtypes in relationship to treatment. These results may be useful for the therapeutic management of individuals infected with HIV-1 non-B strains.
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