Aplicação de metodologia dosimétrica de feixes terapêuticos de raios X com sistema Tandem

Um sistema Tandem, constituído por um par de câmaras de ionização comerciais (uma cilíndrica e uma de placas paralelas), foi estabelecido para aplicação em instituição hospitalar, em substituição ao procedimento convencional de determinação de camadas semi-redutoras utilizando-se absorvedores. Os resultados obtidos mostram a possibilidade de utilização deste sistema em procedimentos de dosimetria para os feixes de ortovoltagem utilizados em radioterapia, como complemento de um programa de controle de qualidade.

Short-Term Heparin Kinetics during Catheter Ablation of Atrial Fibrillation.

BACKGROUND: Percutaneous catheter ablation of atrial fibrillation (CA-AF) is a treatment option for symptomatic drug-refractory atrial fibrillation (AF). CA-AF carries a risk for thromboembolic complications that has been minimized by the use of intraprocedural intravenous unfractionated heparin (UFH). The optimal administration of UFH as well as its kinetics are not well established and need to be precisely determined. METHODS AND RESULTS: A total 102 of consecutive patients suffering from symptomatic drug-refractory AF underwent CA-AF. The mean age was 61 ± 10 years old. After transseptal puncture of the fossa ovalis, weight-adjusted UFH bolus (100 U/kg) was infused. A significant increase in activated clotting time (ACT) was observed from an average value of 100 ± 27 seconds at baseline, to 355 ± 94 seconds at 10 min (T10), to 375 ± 90 seconds at 20 min (T20). Twenty-four patients failed to reach the targeted ACT value of ≥300 seconds at T10 and more than half of these remained with subtherapeutic ACT values at T20. This subset of patients showed similar clinical characteristics and amount of UFH but were more frequently prescribed preprocedural vitamin K1 than the rest of the study population. CONCLUSIONS: In a typical intervention setting, UFH displays unexpected slow anticoagulation kinetics in a significant proportion of procedures up to 20 minutes after infusion. These findings support the infusion of UFH before transseptal puncture or any left-sided catheterization with early ACT measurements to identify patients with delayed kinetics. They are in line with recent guidelines to perform CA-AF under therapeutic anticoagulation.

Characterization of hepatic fatty acids in mice with reduced liver fat by ultra-short echo time (1)H-MRS at 14.1 T in vivo.

Alterations in the hepatic lipid content (HLC) and fatty acid composition are associated with disruptions in whole body metabolism, both in humans and in rodent models, and can be non-invasively assessed by (1)H-MRS in vivo. We used (1)H-MRS to characterize the hepatic fatty-acyl chains of healthy mice and to follow changes caused by streptozotocin (STZ) injection. Using STEAM at 14.1 T with an ultra-short TE of 2.8 ms, confounding effects from T2 relaxation and J-coupling were avoided, allowing for accurate estimations of the contribution of unsaturated (UFA), saturated (SFA), mono-unsaturated (MUFA) and poly-unsaturated (PUFA) fatty-acyl chains, number of double bonds, PU bonds and mean chain length. Compared with in vivo (1) H-MRS, high resolution NMR performed in vitro in hepatic lipid extracts reported longer fatty-acyl chains (18 versus 15 carbons) with a lower contribution from UFA (61 ± 1% versus 80 ± 5%) but a higher number of PU bonds per UFA (1.39 ± 0.03 versus 0.58 ± 0.08), driven by the presence of membrane species in the extracts. STZ injection caused a decrease of HLC (from 1.7 ± 0.3% to 0.7 ± 0.1%), an increase in the contribution of SFA (from 21 ± 2% to 45 ± 6%) and a reduction of the mean length (from 15 to 13 carbons) of cytosolic fatty-acyl chains. In addition, SFAs were also likely to have increased in membrane lipids of STZ-induced diabetic mice, along with a decrease of the mean chain length. These studies show the applicability of (1)H-MRS in vivo to monitor changes in the composition of the hepatic fatty-acyl chains in mice even when they exhibit reduced HLC, pointing to the value of this methodology to evaluate lipid-lowering interventions in the scope of metabolic disorders.

Short stature and primary ovarian insufficiency possibly due to chromosomal position effect in a balanced X;1 translocation.

BACKGROUND: Primary ovarian insufficiency (POI) is defined as a primary ovarian defect characterized by absent menarche (primary amenorrhea), a decrease in the initial primordial follicle number, high follicle-stimulating hormone (FSH) levels and hypoestrogenism. Although the etiology of a majority of POI cases is not yet identified, several data suggest that POI has a strong genetic component. Conventional cytogenetic and molecular analyses have identified regions of the X chromosome that are associated with ovarian function, as well as POI candidate genes, such as FMR1 and DIAPH2. Here we describe a 10.5-year-old girl presenting with high FSH and luteinizing hormone (LH) levels, pathologic GH stimulation arginine and clonidine tests, short stature, pterygium, ovarian dysgenesis, hirsutism and POI. RESULTS: Cytogenetic analysis demonstrated a balanced reciprocal translocation between the q arms of chromosomes X and 1, with breakpoints falling in Xq21 and 1q41 bands. Molecular studies did not unravel any chromosome microdeletion/microduplication, and no XIST-mediated inactivation was found on the derivative chromosome 1. Interestingly, through immunofluorescence assays, we found that part of the Xq21q22 trait, translocated to chromosome 1q41, was late replicating and therefore possibly inactivated in 30 % metaphases both in lymphocytes and skin fibroblasts, in addition to a skewed 100 % inactivation of the normal X chromosome. These findings suggest that a dysregulation of gene expression might occur in this region. Two genes mapping to the Xq translocated region, namely DIAPH2 and FMR1, were found overexpressed if compared with controls. CONCLUSIONS: We report a case in which gonadal dysgenesis and POI are associated with over-expression of DIAPH2 gene and of FMR1 gene in wild type form. We hypothesize that this over-expression is possibly due to a phenomenon known as "chromosomal position effect", which accounts for gene expression variations depending on their localization within the nucleus. For the same effect a double mosaic inactivation of genes mapping to the Xq21-q22 region, demonstrated by immunofluorescence assays, may be the cause of a functional Xq partial monosomy leading to most Turner traits of the proband's phenotype.

Incidence and consequence of major bleeding in primary percutaneous intervention for ST-elevation myocardial infarction in the era of radial access: an analysis of the international randomized Acute myocardial infarction Treated with primary angioplasty and intravenous enoxaparin Or unfractionated heparin to Lower ischemic and bleeding events at short- and Long-term follow-up trial.

AIMS: The aims of the study are to compare the outcome with and without major bleeding and to identify the independent correlates of major bleeding complications and mortality in patients described in the ATOLL study. METHODS: The ATOLL study included 910 patients randomly assigned to either 0.5 mg/kg intravenous enoxaparin or unfractionated heparin before primary percutaneous coronary intervention. Incidence of major bleeding and ischemic end points was assessed at 1 month, and mortality, at 1 and 6 months. Patients with and without major bleeding complication were compared. A multivariate model of bleeding complications at 1 month and mortality at 6 months was realized. Intention-to-treat and per-protocol analyses were performed. RESULTS: The most frequent bleeding site appears to be the gastrointestinal tract. Age >75 years, cardiac arrest, and the use of insulin or >1 heparin emerged as independent correlates of major bleeding at 1 month. Patients presenting with major bleeding had significantly higher rates of adverse ischemic complications. Mortality at 6 months was higher in bleeders. Major bleeding was found to be one of the independent correlates of 6-month mortality. The addition or mixing of several anticoagulant drugs was an independent factor of major bleeding despite the predominant use of radial access. CONCLUSIONS: This study shows that major bleeding is independently associated with poor outcome, increasing ischemic events, and mortality in primary percutaneous coronary intervention performed mostly with radial access.

Drug-eluting stents compared to bare-metal stents improve short-term survival in patients with acute myocardial infarction undergoing primary percutaneous coronary intervention: a nationwide prospective analysis of the AMIS Plus registry.

BACKGROUND: Recently, it has been suggested that the type of stent used in primary percutaneous coronary interventions (pPCI) might impact upon the outcomes of patients with acute myocardial infarction (AMI). Indeed, drug-eluting stents (DES) reduce neointimal hyperplasia compared to bare-metal stents (BMS). Moreover, the later generation DES, due to its biocompatible polymer coatings and stent design, allows for greater deliverability, improved endothelial healing and therefore less restenosis and thrombus generation. However, data on the safety and performance of DES in large cohorts of AMI is still limited. AIM: To compare the early outcome of DES vs. BMS in AMI patients. METHODS: This was a prospective, multicentre analysis containing patients from 64 hospitals in Switzerland with AMI undergoing pPCI between 2005 and 2013. The primary endpoint was in-hospital all-cause death, whereas the secondary endpoint included a composite measure of major adverse cardiac and cerebrovascular events (MACCE) of death, reinfarction, and cerebrovascular event. RESULTS: Of 20,464 patients with a primary diagnosis of AMI and enrolled to the AMIS Plus registry, 15,026 were referred for pPCI and 13,442 received stent implantation. 10,094 patients were implanted with DES and 2,260 with BMS. The overall in-hospital mortality was significantly lower in patients with DES compared to those with BMS implantation (2.6% vs. 7.1%,p < 0.001). The overall in-hospital MACCE after DES was similarly lower compared to BMS (3.5% vs. 7.6%, p < 0.001). After adjusting for all confounding covariables, DES remained an independent predictor for lower in-hospital mortality (OR 0.51,95% CI 0.40-0.67, p < 0.001). Since groups differed as regards to baseline characteristics and pharmacological treatment, we performed a propensity score matching (PSM) to limit potential biases. Even after the PSM, DES implantation remained independently associated with a reduced risk of in-hospital mortality (adjusted OR 0.54, 95% CI 0.39-0.76, p < 0.001). CONCLUSIONS: In unselected patients from a nationwide, real-world cohort, we found DES, compared to BMS, was associated with lower in-hospital mortality and MACCE. The identification of optimal treatment strategies of patients with AMI needs further randomised evaluation; however, our findings suggest a potential benefit with DES.

Blood monitoring of perfluorocarbon compounds (F-tert-butylcyclohexane, perfluoromethyldecalin and perfluorodecalin) by headspace-gas chromatography-tandem mass spectrometry.

A headspace-gas chromatography-tandem mass spectrometry (HS-GC-MS/MS) method for the trace measurement of perfluorocarbon compounds (PFCs) in blood was developed. Due to oxygen carrying capabilities of PFCs, application to doping and sports misuse is speculated. This study was therefore extended to perform validation methods for F-tert-butylcyclohexane (Oxycyte(®)), perfluoro(methyldecalin) (PFMD) and perfluorodecalin (PFD). The limit of detection of these compounds was established and found to be 1.2µg/mL blood for F-tert-butylcyclohexane, 4.9µg/mL blood for PFMD and 9.6µg/mL blood for PFD. The limit of quantification was assumed to be 12µg/mL blood (F-tert-butylcyclohexane), 48µg/mL blood (PFMD) and 96µg/mL blood (PFD). HS-GC-MS/MS technique allows detection from 1000 to 10,000 times lower than the estimated required dose to ensure a biological effect for the investigated PFCs. Thus, this technique could be used to identify a PFC misuse several hours, maybe days, after the injection or the sporting event. Clinical trials with those compounds are still required to evaluate the validation parameters with the calculated estimations.

Short-term HIIT and Fatmax training increase aerobic and metabolic fitness in men with class II and III obesity.

OBJECTIVE: To compare the effects of two different 2-week-long training modalities [continuous at the intensity eliciting the maximal fat oxidation (Fatmax ) versus high-intensity interval training (HIIT)] in men with class II and III obesity. METHODS: Nineteen men with obesity (BMI ≥ 35 kg(.) m(-2) ) were assigned to Fatmax group (GFatmax ) or to HIIT group (GHIIT ). Both groups performed eight cycling sessions matched for mechanical work. Aerobic fitness and fat oxidation rates (FORs) during exercise were assessed prior and following the training. Blood samples were drawn to determine hormones and plasma metabolites levels. Insulin resistance was assessed by the homeostasis model assessment of insulin resistance (HOMA2-IR). RESULTS: Aerobic fitness and FORs during exercise were significantly increased in both groups after training (P ≤ 0.001). HOMA2-IR was significantly reduced only for GFatmax (P ≤ 0.001). Resting non-esterified fatty acids (NEFA) and insulin decreased significantly only in GFatmax (P ≤ 0.002). CONCLUSIONS: Two weeks of HIIT and Fatmax training are effective for the improvement of aerobic fitness and FORs during exercise in these classes of obesity. The decreased levels of resting NEFA only in GFatmax may be involved in the decreased insulin resistance only in this group.

Development of an enantioselective assay for simultaneous separation of venlafaxine and O-desmethylvenlafaxine by micellar electrokinetic chromatography-tandem mass spectrometry: Application to the analysis of drug-drug interaction.

To-date, there has been no effective chiral capillary electrophoresis-mass spectrometry (CE-MS) method reported for the simultaneous enantioseparation of the antidepressant drug, venlafaxine (VX) and its structurally-similar major metabolite, O-desmethylvenlafaxine (O-DVX). This is mainly due to the difficulty of identifying MS compatible chiral selector, which could provide both high enantioselectivity and sensitive MS detection. In this work, poly-sodium N-undecenoyl-L,L-leucylalaninate (poly-L,L-SULA) was employed as a chiral selector after screening several dipeptide polymeric chiral surfactants. Baseline separation of both O-DVX and VX enantiomers was achieved in 15min after optimizing the buffer pH, poly-L,L-SULA concentration, nebulizer pressure and separation voltage. Calibration curves in spiked plasma (recoveries higher than 80%) were linear over the concentration range 150-5000ng/mL for both VX and O-DVX. The limit of detection (LOD) was found to be as low as 30ng/mL and 21ng/mL for O-DVX and VX, respectively. This method was successfully applied to measure the plasma concentrations of human volunteers receiving VX or O-DVX orally when co-administered without and with indinivar therapy. The results suggest that micellar electrokinetic chromatography electrospray ionization-tandem mass spectrometry (MEKC-ESI-MS/MS) is an effective low cost alternative technique for the pharmacokinetics and pharmacodynamics studies of both O-DVX and VX enantiomers. The technique has potential to identify drug-drug interaction involving VX and O-DVX enantiomers while administering indinivar therapy.

On Short Exponential Sums Involving Fourier Coefficients of Holomorphic Cusp Forms

By an exponential sum of the Fourier coefficients of a holomorphic cusp form we mean the sum which is formed by first taking the Fourier series of the said form,then cutting the beginning and the tail away and considering the remaining sum on the real axis. For simplicity’s sake, typically the coefficients are normalized. However, this isn’t so important as the normalization can be done and removed simply by using partial summation. We improve the approximate functional equation for the exponential sums of the Fourier coefficients of the holomorphic cusp forms by giving an explicit upper bound for the error term appearing in the equation. The approximate functional equation is originally due to Jutila [9] and a crucial tool for transforming sums into shorter sums. This transformation changes the point of the real axis on which the sum is to be considered. We also improve known upper bounds for the size estimates of the exponential sums. For very short sums we do not obtain any better estimates than the very easy estimate obtained by multiplying the upper bound estimate for a Fourier coefficient (they are bounded by the divisor function as Deligne [2] showed) by the number of coefficients. This estimate is extremely rough as no possible cancellation is taken into account. However, with small sums, it is unclear whether there happens any remarkable amounts of cancellation.

A short screener is valid for assessing mediterranean diet adherence among older spanish men and women

Ensuring the accuracy of dietary assessment instruments is paramount for interpreting diet-disease relationships. The present study assessed the relative and construct validity of the 14-point Mediterranean Diet Adherence Screener (MEDAS) used in the Prevencio´n con Dieta Mediterra´nea (PREDIMED) study, a primary prevention nutrition-intervention trial. A validated FFQ and the MEDAS were administered to 7146 participants of the PREDIMED study. The MEDASderived PREDIMED score correlated significantly with the corresponding FFQ PREDIMED score (r = 0.52; intraclass correlation coefficient = 0.51) and in the anticipated directions with the dietary intakes reported on the FFQ. Using Bland Altman"s analysis, the average MEDAS Mediterranean diet score estimate was 105% of the FFQ PREDIMED score estimate. Limits of agreement ranged between 57 and 153%. Multiple linear regression analyses revealed that a higher PREDIMED score related directly (P , 0.001) to HDL-cholesterol (HDL-C) and inversely (P , 0.038) to BMI, waist circumference, TG, the TG:HDL-C ratio, fasting glucose, and the cholesterol:HDL-C ratio. The 10-y estimated coronary artery disease risk decreased as the PREDIMED score increased (P , 0.001). The MEDAS is a valid instrument for rapid estimation of adherence to the Mediterranean diet and may be useful in clinical practice.

A short screener is valid for assessing mediterranean diet adherence among older spanish men and women

Ensuring the accuracy of dietary assessment instruments is paramount for interpreting diet-disease relationships. The present study assessed the relative and construct validity of the 14-point Mediterranean Diet Adherence Screener (MEDAS) used in the Prevencio´n con Dieta Mediterra´nea (PREDIMED) study, a primary prevention nutrition-intervention trial. A validated FFQ and the MEDAS were administered to 7146 participants of the PREDIMED study. The MEDASderived PREDIMED score correlated significantly with the corresponding FFQ PREDIMED score (r = 0.52; intraclass correlation coefficient = 0.51) and in the anticipated directions with the dietary intakes reported on the FFQ. Using Bland Altman"s analysis, the average MEDAS Mediterranean diet score estimate was 105% of the FFQ PREDIMED score estimate. Limits of agreement ranged between 57 and 153%. Multiple linear regression analyses revealed that a higher PREDIMED score related directly (P , 0.001) to HDL-cholesterol (HDL-C) and inversely (P , 0.038) to BMI, waist circumference, TG, the TG:HDL-C ratio, fasting glucose, and the cholesterol:HDL-C ratio. The 10-y estimated coronary artery disease risk decreased as the PREDIMED score increased (P , 0.001). The MEDAS is a valid instrument for rapid estimation of adherence to the Mediterranean diet and may be useful in clinical practice.