Prevalence and Predictors of Potential Drug-Drug Interactions in the Elderly: A Cross-Sectional Study in the Brazilian Primary Public Health System

Purpose. The primary objective of this study was to investigate the prevalence of clinically important potential drug-drug interactions (DDIs) in elderly patients attending the public primary health care system in Brazil. The secondary objective was to investigate possible predictors of potential DDIs. Methods. A cross-sectional study was carried out in 5 Brazilian cities located in the Ourinhos Micro-region, Sao Paulo State, between November 2010 and April 2011. The selected sample was divided according to the presence (exposed) or absence (unexposed) of one or more potential DDIs (defined as the presence of a minimum 5-day overlap in supply of an interacting drug pair). Data were collected from medical prescriptions and patients' medical records. Potential DDIs (rated major or moderate) were identified using 4 DDI-checker programs. Logistic regression analysis was used to study potential DDI predictors. Results. The prevalence of clinically important potential DDIs found during the study period was 47.4%. Female sex (OR = 2.49 [95% CI 2.29-2.75]), diagnosis of = 3 diseases (OR = 6.43 [95% CI 3.25-12.44]), and diagnosis of hypertension (OR = 1.68 [95% CI 1.23-2.41]) were associated with potential DDIs. The adjusted OR increased from 0.90 [95% CI 0.82-1.03] in patients aged 60 - 64 years to 4.03 [95% CI 3.79 - 4.28] in those aged 75 years or older. Drug therapy regimens involving = 2 prescribers (OR = 1.39 [95% CI 1.17-1.67]), = 3 drugs (OR = 3.21 [95% CI 2.78-3.59]), = 2 ATC codes (OR = 1.19 [95% CI 1.12-1.29]), = 2 drugs acting on cytochrome P450 (OR = 2.24 [95% CI 2.07-2.46]), and ATC codes B (OR = 1.89 [95% CI 1.05-2.08]) and C (OR = 4.01 [95% CI 3.55-4.57]) were associated with potential DDIs. Conclusion. Special care should be taken with the prescription and therapeutic follow-up of patients who present characteristics identified as predictors. Knowledge of potential DDI predictors could aid in developing preventive practices and policies that allow public health services to better manage this situation.

From Sample Processing to Quantification: A Full Electrochemical Approach for Neutral Analyte Derivatization, Capillary Electrophoresis Separation, and Contactless Conductivity Detection

A thin-layer electrochemical flow cell coupled to capillary electrophoresis with contactless conductivity detection (EC-CE-(CD)-D-4) was applied for the first time to the derivatization and quantification of neutral species using aliphatic alcohols as model compounds. The simultaneous electrooxidation of four alcohols (ethanol, 1-propanol, 1-butanol, and 1-pentanol) to the corresponding carboxylates was carried out on a platinum working electrode in acid medium. The derivatization step required 1 min at 1.6 V vs. Ag/AgCl under stopped flow conditions, which was preceded by a 10 s activation at 0 V. The solution close to the electrode surface was then hydrodynamically injected into the capillary, and a 2.5 min electrophoretic separation was carried out. The fully automated flow system operated at a frequency of 12 analyses per hour. Simultaneous determination of the four alcohols presented detection limits of about 5 x 10(-5) mol As a practical application with a complex matrix, ethanol concentrations were determined in diluted pale lager beer and in nonalcoholic beer. No statistically significant difference was observed between the EC-CE-(CD)-D-4 and gas chromatography with flame ionization detection (GC-FID) results for these samples. The derivatization efficiency remained constant over several hours of continuous operation with lager beer samples (n = 40).

The chemiluminescent peroxyoxalate system: state of the art almost 50 years from its discovery

Almost fifty years after the discovery of the peroxyoxalate reaction by E. A. Chandross in the early nineteen sixties, this review article intends to give a general overview on mechanistic aspects of this system and to describe the principles of its analytical application. After a short general introduction on the principles of chemiluminescence and the history of peroxyoxalate discovery, mechanistic aspects of high-energy intermediate formation, its structure and its reaction with an activator in the peroxyoxalate system are discussed. Finally, analytical applications of peroxyoxalate chemiluminescence are exemplified using representative recent examples, including oxalic acid detection in biological samples.

Introduction to the Software-defined Radio Approach

Telecommunications have been in constant evolution during past decades. Among the technological innovations, the use of digital technologies is very relevant. Digital communication systems have proven their efficiency and brought a new element in the chain of signal transmitting and receiving, the digital processor. This device offers to new radio equipments the flexibility of a programmable system. Nowadays, the behavior of a communication system can be modified by simply changing its software. This gave rising to a new radio model called Software Defined Radio (or Software-Defined Radio - SDR). In this new model, one moves to the software the task to set radio behavior, leaving to hardware only the implementation of RF front-end. Thus, the radio is no longer static, defined by their circuits and becomes a dynamic element, which may change their operating characteristics, such as bandwidth, modulation, coding rate, even modified during runtime according to software configuration. This article aims to present the use of GNU Radio software, an open-source solution for SDR specific applications, as a tool for development configurable digital radio.

JC virus-associated central nervous system diseases in HIV-infected patients in Brazil: clinical presentations, associated factors with mortality and outcome

Introduction: Several presentations of neurologic complications caused by JC virus (JCV) in human immunodeficiency virus (HIV)-infected patients have been described and need to be distinguished from the "classic" form of progressive multifocal leukoencephalopathy (PML). The objectives of this study were: 1) to describe the spectrum and frequency of presentations of JCV-associated central nervous system (CNS) diseases; 2) identify factors associated with in-hospital mortality of patients with JCV-associated CNS disease; and 3) to estimate the overall mortality of this population. Material and methods: This was a retrospective study of HIV-infected patients admitted consecutively for JCV-associated CNS diseases in a referral teaching center in Sao Paulo, Brazil, from 2002 to 2007. All patients with laboratory confirmed JCV-associated CNS diseases were included using the following criteria: compatible clinical and radiological features associated with the presence of JCV DNA in the cerebrospinal fluid. JCV-associated CNS diseases were classified as follows: 1) classic PML; 2) inflammatory PML; and 3) JC virus granule cell neuronopathy (GCN). Results: We included 47 cases. JCV-associated CNS diseases were classified as follows: 1) classic PML: 42 (89%); 2) inflammatory PML: three (6%); and 3) JC virus GCN: four (9%). Nosocomial pneumonia (p = 0.003), previous diagnosis of HIV infection (p = 0.03), and imaging showing cerebellar and/or brainstem involvement (p = 0.02) were associated with in-hospital mortality. Overall mortality during hospitalization was 34%. Conclusions: Novel presentations of JCV-associated CNS diseases were observed in our setting; nosocomial pneumonia, previous diagnosis of HIV infection, and cerebellar and/or brainstem involvement were associated with in-hospital mortality; and overall mortality was high. (C) 2012 Elsevier Editora Ltda. All rights reserved.

Mating system parameters at hierarchical levels of fruits, individuals and populations in the Brazilian insect-pollinated tropical tree, Tabebuia roseo-alba (Bignoniaceae)

For many tree species, mating system analyses have indicated potential variations in the selfing rate and paternity correlation among fruits within individuals, among individuals within populations, among populations, and from one flowering event to another. In this study, we used eight microsatellite markers to investigate mating systems at two hierarchical levels (fruits within individuals and individuals within populations) for the insect pollinated Neotropical tree Tabebuia roseo-alba. We found that T. roseo-alba has a mixed mating system with predominantly outcrossed mating. The outcrossing rates at the population level were similar across two T. roseo-alba populations; however, the rates varied considerably among individuals within populations. The correlated paternity results at different hierarchical levels showed that there is a high probability of shared paternal parentage when comparing seeds within fruits and among fruits within plants and full-sibs occur in much higher proportion within fruits than among fruits. Significant levels of fixation index were found in both populations and biparental inbreeding is believed to be the main cause of the observed inbreeding. The number of pollen donors contributing to mating was low. Furthermore, open-pollinated seeds varied according to relatedness, including half-sibs, full-sibs, self-sibs and self- half-sibs. In both populations, the effective population size within a family (seed-tree and its offspring) was lower than expected for panmictic populations. Thus, seeds for ex situ conservation genetics, progeny tests and reforestation must be collected from a large number of seed-trees to guarantee an adequate effective population in the sample.

Quality characteristics and fertilizing ability of ram sperm subpopulations separated by partition in an aqueous two-phase system

Centrifugal countercurrent distribution (CCCD) in an aqueous two-phase system (TPS) is a resolute technique revealing sperm heterogeneity and for the estimation of the fertilizing potential of a given semen sample. However, separated sperm subpopulations have never been tested for their fertilizing ability yet. Here, we have compared sperm quality parameters and the fertilizing ability of sperm subpopulations separated by the CCCD process from ram semen samples maintained at 20 degrees C or cooled down to 5 degrees C. Total and progressive sperm motility was evaluated by computer-assisted analysis using a CASA system and membrane integrity was evaluated by flow cytometry by staining with CFDA/Pl. The capacitation state, staining with chlortetracycline, and apoptosis-related markers, such as phosphatidylserine (PS) translocation detected with Annexin V. and DNA damage detected by the TUNEL assay, were determined by fluorescence microscopy. Additionally, the fertilizing ability of the fractionated subpopulations was comparative assessed by zona binding assay (ZBA). CCCD analysis revealed that the number of spermatozoa displaying membrane and DNA alterations was higher in samples chilled at 5 degrees C than at 20 degrees C. which can be reflected in the displacement to the left of the CCCD profiles. The spermatozoa located in the central and right chambers (more hydrophobic) presented higher values (P<0.01) of membrane integrity, lower PS translocation (P<0.05) and DNA damage (P<0.001) than those in the left part of the profile, where apoptotic markers were significantly increased and the proportion of viable non-capacitated sperm was reduced. We have developed a new protocol to recover spermatozoa from the CCCD fractions and we proved that these differences were related with the fertilizing ability determined by ZBA, because we found that the number of spermatozoa attached per oocyte was significantly higher for spermatozoa recovered from the central and right chambers, in both types of samples. This is the first time, to our knowledge that sperm recovered from a two-phase partition procedure are used for fertilization assays. These results open up new possibilities for using specific subpopulations of sperm for artificial insemination or in vitro fertilization, not only regarding better sperm quality but also certain characteristics such as subpopulations enriched in spermatozoa bearing X or Y chromosome that we have already isolated or any other feature. (C) 2011 Elsevier B.V. All rights reserved.

Evaluation of physiologic complexity in time series using generalized sample entropy and surrogate data analysis

Complexity in time series is an intriguing feature of living dynamical systems, with potential use for identification of system state. Although various methods have been proposed for measuring physiologic complexity, uncorrelated time series are often assigned high values of complexity, errouneously classifying them as a complex physiological signals. Here, we propose and discuss a method for complex system analysis based on generalized statistical formalism and surrogate time series. Sample entropy (SampEn) was rewritten inspired in Tsallis generalized entropy, as function of q parameter (qSampEn). qSDiff curves were calculated, which consist of differences between original and surrogate series qSampEn. We evaluated qSDiff for 125 real heart rate variability (HRV) dynamics, divided into groups of 70 healthy, 44 congestive heart failure (CHF), and 11 atrial fibrillation (AF) subjects, and for simulated series of stochastic and chaotic process. The evaluations showed that, for nonperiodic signals, qSDiff curves have a maximum point (qSDiff(max)) for q not equal 1. Values of q where the maximum point occurs and where qSDiff is zero were also evaluated. Only qSDiff(max) values were capable of distinguish HRV groups (p-values 5.10 x 10(-3); 1.11 x 10(-7), and 5.50 x 10(-7) for healthy vs. CHF, healthy vs. AF, and CHF vs. AF, respectively), consistently with the concept of physiologic complexity, and suggests a potential use for chaotic system analysis. (C) 2012 American Institute of Physics. [http://dx.doi.org/10.1063/1.4758815]

Phase-Locked loops lock-in range in Frequency Modulated-Atomic Force Microscope nonlinear control system

Since the mid 1980s the Atomic Force Microscope is one the most powerful tools to perform surface investigation, and since 1995 Non-Contact AFM achieved true atomic resolution. The Frequency-Modulated Atomic Force Microscope (FM-AFM) operates in the dynamic mode, which means that the control system of the FM-AFM must force the micro-cantilever to oscillate with constant amplitude and frequency. However, tip-sample interaction forces cause modulations in the microcantilever motion. A Phase-Locked loop (PLL) is used to demodulate the tip-sample interaction forces from the microcantilever motion. The demodulated signal is used as the feedback signal to the control system, and to generate both topographic and dissipation images. As a consequence, a proper design of the PLL is vital to the FM-AFM performance. In this work, using bifurcation analysis, the lock-in range of the PLL is determined as a function of the frequency shift (Q) of the microcantilever and of the other design parameters, providing a technique to properly design the PLL in the FM-AFM system. (C) 2011 Elsevier B.V. All rights reserved.

The impact of the CACNA1C risk allele on limbic structures and facial emotions recognition in bipolar disorder subjects and healthy controls

Introduction: Impairments in facial emotion recognition (PER) have been reported in bipolar disorder (BD) during all mood states. FER has been the focus of functional magnetic resonance imaging studies evaluating differential activation of limbic regions. Recently, the alpha 1-C subunit of the L-type voltage-gated calcium channel (CACNA1C) gene has been described as a risk gene for BD and its Met allele found to increase CACNA1C mRNA expression. In healthy controls, the CACNA1C risk (Met) allele has been reported to increase limbic system activation during emotional stimuli and also to impact on cognitive function. The aim of this study was to investigate the impact of CACNA1C genotype on FER scores and limbic system morphology in subjects with BD and healthy controls. Material and methods: Thirty-nine euthymic BD I subjects and 40 healthy controls were submitted to a PER recognition test battery and genotyped for CACNA1C. Subjects were also examined with a 3D 3-Tesla structural imaging protocol. Results: The CACNA1C risk allele for BD was associated to FER impairment in BD, while in controls nothing was observed. The CACNA1C genotype did not impact on amygdala or hippocampus volume neither in BD nor controls. Limitations: Sample size. Conclusion: The present findings suggest that a polymorphism in calcium channels interferes FER phenotype exclusively in BD and doesn't interfere on limbic structures morphology. (C) 2012 Elsevier B.V. All rights reserved.

Ubiquitin proteasome system and the atypical kinase PfPK7 are involved in melatonin signaling in Plasmodium falciparum

We previously reported that melatonin modulates the Plasmodium falciparum erythrocytic cycle by increasing schizont stage population as well as diminishing ring stage population. In addition, the importance of calcium and cAMP in melatonin signaling pathway in P. falciparum was also demonstrated. Nevertheless, the molecular effectors of the indoleamine signaling pathway remain elusive. We now demonstrate by real-time PCR that melatonin treatment up-regulates genes related to ubiquitin/proteasome system (UPS) components and that luzindole, a melatonin receptor antagonist, inhibits UPS transcription modulation. We also show that protein kinase PfPK7, a P. falciparum orphan kinase, plays a crucial role in the melatonin transduction pathway, since following melatonin treatment of P. falciparum parasites where pfpk7 gene is disrupted (pfpk7- parasites) (i) the ratio of asexual stages remain unchanged, (ii) the increase in cytoplasmatic calcium in response to melatonin was strongly diminished and (iii) up-regulation of UPS genes did not occur. The wild-type melatonin-induced alterations in cell cycle features, calcium rise and UPS gene transcription were restored by re-introduction of a functional copy of the pfpk7 gene in the pfpk7- parasites.

Spontaneous combined rupture of a pelvicalyceal cyst into the collector system and retroperitoneal space during the acquisition of computed tomography scan images: a case report

Abstract Introduction Pelvicalyceal cysts are common findings in autopsies and can manifest with a variety of patterns. These cystic lesions are usually a benign entity with no clinical significance unless they enlarge enough to cause compression of the adjacent collecting system and consequently obstructive uropathy. Few cases of the spontaneous rupture of pelvicalyceal renal cysts have been published and to the best of our knowledge there is no report of a combined rupture to collector system and retroperitoneal space documented during a multiphase computed tomography. Case presentation We report a case of a ‘real-time’ spontaneous rupture of a pelvicalyceal cyst into the collecting system with fistulization into the retroperitoneum. The patient was a 78-year-old Caucasian man with a previous history of renal stones and a large pelvicalyceal renal cyst who was admitted to our Emergency department with acute right flank pain. A multiphase computed tomography was performed and the pre-contrast images demonstrated a right pelvicalyceal renal cyst measuring 12.0 × 6.1cm in the lower pole causing moderate dilation of the upper right renal collection system. In addition, a partially obstructive stone on the left distal ureter with mild left hydronephrosis was noted. The nephrographic phase did not add any new information. The excretory phase (10-minute delay) demonstrated a spontaneous rupture of the cyst into the pelvicalyceal system with posterior fistulization into the retroperitoneal space. Conclusion In this case study we present time-related changes of a rare pelvicalyceal cyst complication, which to the best of our knowledge has fortunately not been previously documented. Analysis of the sequential images and comparison with an earlier scan allowed us to better understand the physiopathological process of the rupture, the clinical presentation and to elaborate hypotheses for its etiopathogenesis.

Classical bifurcation in a quadrupolar NMR system

The Josephson junction model is applied to the experimental implementation of classical bifurcation in a quadrupolar nuclear magnetic resonance system. There are two regimes, one linear and one nonlinear, which are implemented by the radio-frequency and the quadrupolar terms of the Hamiltonian of a spin system, respectively. These terms provide an explanation of the symmetry breaking due to bifurcation. Bifurcation depends on the coexistence of both regimes at the same time in different proportions. The experiment is performed on a lyotropic liquid crystal sample of an ordered ensemble of 133Cs nuclei with spin I = 7/2 at room temperature. Our experimental results confirm that bifurcation happens independently of the spin value and of the physical system. With this experimental spin scenario, we confirm that a quadrupolar nuclei system could be described analogously to a symmetric two-mode Bose-Einstein condensate.