Sensitivity, specificity and predictive values of linear and nonlinear indices of heart rate variability in stable angina patients

Background: Decreased heart rate variability (HRV) is related to higher morbidity and mortality. In this study we evaluated the linear and nonlinear indices of the HRV in stable angina patients submitted to coronary angiography. Methods. We studied 77 unselected patients for elective coronary angiography, which were divided into two groups: coronary artery disease (CAD) and non-CAD groups. For analysis of HRV indices, HRV was recorded beat by beat with the volunteers in the supine position for 40 minutes. We analyzed the linear indices in the time (SDNN [standard deviation of normal to normal], NN50 [total number of adjacent RR intervals with a difference of duration greater than 50ms] and RMSSD [root-mean square of differences]) and frequency domains ultra-low frequency (ULF) ≤ 0,003 Hz, very low frequency (VLF) 0,003 - 0,04 Hz, low frequency (LF) (0.04-0.15 Hz), and high frequency (HF) (0.15-0.40 Hz) as well as the ratio between LF and HF components (LF/HF). In relation to the nonlinear indices we evaluated SD1, SD2, SD1/SD2, approximate entropy (-ApEn), α1, α2, Lyapunov Exponent, Hurst Exponent, autocorrelation and dimension correlation. The definition of the cutoff point of the variables for predictive tests was obtained by the Receiver Operating Characteristic curve (ROC). The area under the ROC curve was calculated by the extended trapezoidal rule, assuming as relevant areas under the curve ≥ 0.650. Results: Coronary arterial disease patients presented reduced values of SDNN, RMSSD, NN50, HF, SD1, SD2 and -ApEn. HF ≤ 66 ms§ssup§2§esup§, RMSSD ≤ 23.9 ms, ApEn ≤-0.296 and NN50 ≤ 16 presented the best discriminatory power for the presence of significant coronary obstruction. Conclusion: We suggest the use of Heart Rate Variability Analysis in linear and nonlinear domains, for prognostic purposes in patients with stable angina pectoris, in view of their overall impairment. © 2012 Pivatelli et al.; licensee BioMed Central Ltd.

Comparison of Two Staining Methods for Pollen Viability Studies in Sugarcane

The present work aimed to compare two staining methods for pollen viability evaluation in sugarcane. Pollen from four sugarcane genotypes were collected at three different times (6.00, 8.00 and 9.00 a.m.) and tested for viability using two staining methods (iodine and lactophenol blue). Three anthers, of each genotype were crushed in a glass slide with a drop of the respective stain (iodine 0.1 N and lactophenol blue). The percentage of pollen viability was obtained with an optic microscope (250×) and compared with the pollen germination at culture media where one raquis of each genotype was gentle shaken in a petridish. Three replicates (petri dishes) was performed for each genotype which were maintained at the temperature of 25 °C and air humidity around 95 % for 30 min. The factors (staining methods, genotypes and times) and their interactions were evaluated by the analysis of variance, F test (P < 0.01) and the means compared by the t test (P < 0.05). The lactophenol blue staining was more sensible than the iodine staining method to detect the decrease of pollen viability which occurs naturally in sugarcane. The iodine staining method was more stable and easier than lactophenol to perform the inflorescence classification at any evaluated time (6.00, 8.00 and 9.00 a. m.). Both staining methods overestimated the viability obtained by the germination at culture media when performed at 6.00 a.m. © 2012 Society for Sugar Research & Promotion.

A Critical Review of Properties of Darunavir and Analytical Methods for Its Determination

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Stability study of fluconazole applying validated bioassay and stability-indicating LC methods

Chemical degradation of drugs may result in altered therapeutic efficacy and even toxic effects. Therefore, understanding the factors that change the stability of pharmaceuticals and identifying ways to guarantee their stability are important. In this work stability-indicating Liquid Chromatographic (LC) and bioassay methods were validated and employed in the fluconazole stability studies. The correlation of sample results from both methods was evaluated. Fluconazole raw material stability was investigated in aqueous, acid (0.1 M HCl), alkaline (0.1 M NaOH) and oxidative (3% v/v H2O2) reflux for 6 hours, by LC method. Fluconazole capsules were exposed to UVC (254 nm, 66 and 180 days), climatic chamber (40°C, 75% RH, 90 days) and oven (60°C, 60 days), these samples were analyzed by LC and bioassay methods It was found that the drug is degraded (10% decrease) with arising of a possible degradation product in an oxidative medium and UVC exposure, in all the others conditions fluconazole remained chemically stable (higher than 98%) when analyzed by LC. However when the capsules stressed samples were evaluated through bioassay very low antifungal activity was found (about 30%). Fluconazole showed to be an unstable drug and it indicates that special care must be taken during the handling, storage and quality control using appropriated methods to analyze this therapeutic agent. This work suggests monitoring the fluconazole stability by bioassay and the stability-indicating LC methods.

Characteristics, complexation and analytical methods of darunavir

What is it? Darunavir is a protease inhibitor used in the treatment of HIV infection. It is an important drug of therapy cocktail for patients infected with the virus. On the market there are darunavir ethanolate tablets of 75, 150, 300, 400, 600 and 800mg, because this is the most stable form. It is commercialized by Janssen-Cilag with the name PrezistaTM. Why we started? This drug has low water solubility and poor bioavailability, therefore requires administration in doses relatively high to the success of the therapeutic effect. The complexation of drugs by using cyclodextrin is welcome in this respect to improve the solubility and hence increase the dissolution rate of poorly soluble drugs. A monograph about this compound has not been described, thus it is an extremely important quality control of darunavir to demonstrate its effectiveness and safety. What we did? Some existing analytical techniques have been discussed in this manuscript, focusing on bioanalytical and pharmaceutical quality control applications. What we found? This review showed the published analytical methods reported for the determination of darunavir and discuss about its characteristics and complexation with cyclodextrin.

Discrimination of production environments of specialty coffees by means of stable isotopes and discriminant model

The south of Minas Gerais, Brazil stands out among various regions through its capacity for production of specialty coffees. Its potential, manifested through being one of the most award-winning Brazilian regions in recent years, has been recognized by the Cup of Excellence (COE). With the evident relationship between product quality and the environment in mind, the need arises for scientific studies to provide a foundation for discrimination of product origin, creating new methods for combating possible fraud. The aim of this study was to evaluate the use of carbon and nitrogen isotopes in discrimination of production environments of specialty coffees from the Serra da Mantiqueira of Minas Gerais by means of the discriminant model. Coffee samples were composed of ripe yellow and red fruits collected manually at altitudes below 1,000 m, from 1,000 to 1,200 m and above 1,200 m. The yellow and red fruits were subjected to dry processing and wet processing, with five replications. A total of 119 samples were used for discrimination of specialty coffee production environments by means of stable isotopes and statistical modeling. The model generated had an accuracy rate of 89% in discrimination of environments and was composed of the isotope variables of δ15N, δ13C, %C, %N, δD, δ18O (meteoric water) and sensory analysis scores. In addition, for the first time, discrimination of environments on a local geographic scale, within a single municipality, was proposed and successfully concluded. This shows that isotope analysis is an effective method in verifying geographic origin for specialty coffees.

Bioelectrical impedance vector analysis (BIVA) in stable preterm newborns

Objective: To observe the behavior of the plotted vectors on the RXc (R - resistance - and Xc - reactance corrected for body height/length) graph through bioelectrical impedance analysis (BIVA) and phase angle (PA) values in stable premature infants, considering the hypothesis that preterm infants present vector behavior on BIVA suggestive of less total body water and soft tissues, compared to reference data for term infants. Methods: Cross-sectional study, including preterm neonates of both genders, in-patients admitted to an intermediate care unit at a tertiary care hospital. Data on delivery, diet and bioelectrical impedance (800 mA, 50 kHz) were collected. The graphs and vector analysis were performed with the BIVA software. Results: A total of 108 preterm infants were studied, separated according to age (< 7 days and >= 7 days). Most of the premature babies were without the normal range (above the 95% tolerance intervals) existing in literature for term newborn infants and there was a tendency to dispersion of the points in the upper right quadrant, RXc plan. The PA was 4.92 degrees (+/- 2.18) for newborns < 7 days and 4.34 degrees (+/- 2.37) for newborns >= 7 days. Conclusion: Premature infants behave similarly in terms of BIVA and most of them have less absolute body water, presenting less fat free mass and fat mass in absolute values, compared to term newborn infants.

A stable liquid-liquid extraction system for clavulanic acid using polymer-based aqueous two-phase systems

The partitioning of Clavulanic Acid (CA) in a novel inexpensive and stable aqueous two-phase system (ATPS) composed by poly(ethylene glycol) (PEG) and sodium polyacrylate (NaPA) has been studied. The aqueous two-phase systems are formed by mixing both polymers with a salt (NaCl or Na2SO4) and an aqueous solution of CA. The stability of CA on the presence of both polymers was investigated and it was observed that these polymers do not degrade the biomolecule. The effect of PEG-molecular size, polymer concentrations on the commercial CA partitioning has been studied, at 25 degrees C. The data showed that commercial CA was preferentially partitioned for the PEG-rich phase with a partition coefficient (K-CA) between 1 and 12 in the PEG/NaPA aqueous two phase systems supplemented with NaCl and Na2SO4. The partition to the PEG phase was increased in the systems with high polymer concentrations. Furthermore, Na2SO4 caused higher CA preference for the PEG-phase than NaCl. The systems having a composition with 10 wt.% of PEG4000, 20 wt.% of NaPA8000 and 6 wt.% of Na2SO4 were selected as the optimal ones in terms of recovery of CA from fermented broth of Streptomyces clavuligerus. The partitioning results (K-CA = 9.15 +/- 1.06) are competitive with commercial extraction methods of CA (K-CA = 11.91 +/- 2.08) which emphasizes that the system PEG/NaPA/Na2SO4 can be used as a new process to CA purification/concentration from fermented broth. (C) 2012 Elsevier B.V. All rights reserved.

Biomechanical in vitro evaluation of three stable internal fixation techniques used in sagittal osteotomy of the mandibular ramus: a study in sheep mandibles

Among the osteotomies performed in orthognathic surgery, the sagittal osteotomy of the mandibular ramus (SOMR) is the most common, allowing a great range of movements and stable internal fixation (SIF), therefore eliminating the need of maxillomandibular block in the postoperative period. Objectives: The purpose of this study was to evaluate the biomechanical resistance of three national systems used for SIF in SOMR in sheep mandibles. Material and methods: The study was performed in 30 sheep hemi-mandibles randomly divided into 3 experimental groups, each containing 10 hemi-mandibles. The samples were measured to avoid discrepancies and then subjected to SOMR with 5-mm advancement. In group I, 2.0x12 mm screws were used for fixation, inserted in an inverted "L" pattern (inverted "L" group). In group II, fixation was performed with two 2.0x12 mm screws, positioned in a linear pattern and a 4-hole straight miniplate and four 2.0x6.0 mm monocortical screws (hybrid group). In group III, fixation was performed with two-hole straight miniplates and eight 2.0x6.0 mm monocortical screws (mini plate group). All materials used for SIF were supplied by Osteosin - SIN. The hemimandibles were subjected to vertical linear load test by Kratos K2000MP mechanical testing unit for loading registration and displacement. Results: All groups showed similar resistance during mechanical test for loading and displacement, with no statistically significant differences between groups according to analysis of variance. Conclusion: These results indicate that the three techniques of fixation are equally effective for clinical fixation of SOMR.

The effect of acute magnesium loading on the maximal exercise performance of stable chronic obstructive pulmonary disease patients

OBJECTIVE: The potential influence of magnesium on exercise performance is a subject of increasing interest. Magnesium has been shown to have bronchodilatatory properties in asthma and chronic obstructive pulmonary disease patients. The aim of this study was to investigate the effects of acute magnesium IV loading on the aerobic exercise performance of stable chronic obstructive pulmonary disease patients. METHODS: Twenty male chronic obstructive pulmonary disease patients (66.2 +/- 8.3 years old, FEV1: 49.3 +/- 19.8%) received an IV infusion of 2 g of either magnesium sulfate or saline on two randomly assigned occasions approximately two days apart. Spirometry was performed both before and 45 minutes after the infusions. A symptom-limited incremental maximal cardiopulmonary test was performed on a cycle ergometer at approximately 100 minutes after the end of the infusion. ClinicalTrials.gov: NCT00500864 RESULTS: Magnesium infusion was associated with significant reductions in the functional residual capacity (-0.41 l) and residual volume (-0.47 l), the mean arterial blood pressure (-5.6 mmHg) and the cardiac double product (734.8 mmHg.bpm) at rest. Magnesium treatment led to significant increases in the maximal load reached (+8 w) and the respiratory exchange ratio (0.06) at peak exercise. The subgroup of patients who showed increases in the work load equal to or greater than 5 w also exhibited significantly greater improvements in inspiratory capacity (0.29 l). CONCLUSIONS: The acute IV loading of magnesium promotes a reduction in static lung hyperinflation and improves the exercise performance in stable chronic obstructive pulmonary disease patients. Improvements in respiratory mechanics appear to be responsible for the latter finding.

Effect of Complete Revascularization on 10-Year Survival of Patients With Stable Multivessel Coronary Artery Disease MASS II Trial

Background-The importance of complete revascularization remains unclear and contradictory. This current investigation compares the effect of complete revascularization on 10-year survival of patients with stable multivessel coronary artery disease (CAD) who were randomly assigned to percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG). Methods and Results-This is a post hoc analysis of the Second Medicine, Angioplasty, or Surgery Study (MASS II), which is a randomized trial comparing treatments in patients with stable multivessel CAD, and preserved systolic ventricular function. We analyzed patients who underwent surgery (CABG) or stent angioplasty (PCI). The survival free of overall mortality of patients who underwent complete (CR) or incomplete revascularization (IR) was compared. Of the 408 patients randomly assigned to mechanical revascularization, 390 patients (95.6%) underwent the assigned treatment; complete revascularization was achieved in 224 patients (57.4%), 63.8% of those in the CABG group and 36.2% in the PCI group (P = 0.001). The IR group had more prior myocardial infarction than the CR group (56.2% X 39.2%, P = 0.01). During a 10-year follow-up, the survival free of cardiovascular mortality was significantly different among patients in the 2 groups (CR, 90.6% versus IR, 84.4%; P = 0.04). This was mainly driven by an increased cardiovascular specific mortality in individuals with incomplete revascularization submitted to PCI (P = 0.05). Conclusions-Our study suggests that in 10-year follow-up, CR compared with IR was associated with reduced cardiovascular mortality, especially due to a higher increase in cardiovascular-specific mortality in individuals submitted to PCI.

Expression Analysis of Wound Healing Genes in Human Periapical Granulomas of Progressive and Stable Nature

Introduction: Wound healing process involves the activation of extracellular matrix components, remodeling enzymes, cellular adhesion molecules, growth factors, cytokines and chemokines genes. However, the molecular patterns underlying the healing process periapical environment remain unclear. Here we hypothesized that endodontic infection might result in an imbalance in the expression of wound healing genes involved in the pathogenesis of periapical lesions. Furthermore, we suggest that differential expression of wound healing markers in active and latent granulomas could account for different clinical outcomes for such lesions. Methods: Study samples consisted of 93 periapical granulomas collected after endodontic surgeries and 24 healthy periodontal ligament tissues collected from premolars extracted for orthodontic purposes as control samples. Of these, 10 periapical granulomas and 5 healthy periapical tissues were used for expression analysis of 84 wound healing genes by using a pathway-specific real-time polymerase chain reaction array. The remaining 83 granulomas and all 24 control specimens were used to validate the obtained array data by real-time polymerase chain reaction. Observed variations in expression of wound healing genes were analyzed according to the classification of periapical granulomas as active/progressive versus inactive/stable (as determined by receptor activator for nuclear factor kappa B ligand/osteoprotegerin expression ratio). Results: We observed a marked increase of 5-fold or greater in SERPINE1, TIMP1, COL1A1, COL5A1, VTN, CTGF, FGF7, TGFB1, TNF, CXCL11, ITGA4, and ITGA5 genes in the periapical granulomas when compared with control samples. SERPINE1, TIMP1, COL1A1, TGFB1, and ITGA4 mRNA expression was significantly higher in inactive compared with active periapical granulomas (P < .001), whereas TNF and CXCL11 mRNA expression was higher in active lesions (P < .001). Conclusions: The identification of novel gene targets that curb the progression status of periapical lesions might contribute to a more accurate diagnosis and lead to treatment modalities more conducive to endodontic success. (J Endod 2012;38:185-190)

Sensitivity, specificity and predictive values of linear and nonlinear indices of heart rate variability in stable angina patients

Abstract Background Decreased heart rate variability (HRV) is related to higher morbidity and mortality. In this study we evaluated the linear and nonlinear indices of the HRV in stable angina patients submitted to coronary angiography. Methods We studied 77 unselected patients for elective coronary angiography, which were divided into two groups: coronary artery disease (CAD) and non-CAD groups. For analysis of HRV indices, HRV was recorded beat by beat with the volunteers in the supine position for 40 minutes. We analyzed the linear indices in the time (SDNN [standard deviation of normal to normal], NN50 [total number of adjacent RR intervals with a difference of duration greater than 50ms] and RMSSD [root-mean square of differences]) and frequency domains ultra-low frequency (ULF) ≤ 0,003 Hz, very low frequency (VLF) 0,003 – 0,04 Hz, low frequency (LF) (0.04–0.15 Hz), and high frequency (HF) (0.15–0.40 Hz) as well as the ratio between LF and HF components (LF/HF). In relation to the nonlinear indices we evaluated SD1, SD2, SD1/SD2, approximate entropy (−ApEn), α1, α2, Lyapunov Exponent, Hurst Exponent, autocorrelation and dimension correlation. The definition of the cutoff point of the variables for predictive tests was obtained by the Receiver Operating Characteristic curve (ROC). The area under the ROC curve was calculated by the extended trapezoidal rule, assuming as relevant areas under the curve ≥ 0.650. Results Coronary arterial disease patients presented reduced values of SDNN, RMSSD, NN50, HF, SD1, SD2 and -ApEn. HF ≤ 66 ms2, RMSSD ≤ 23.9 ms, ApEn ≤−0.296 and NN50 ≤ 16 presented the best discriminatory power for the presence of significant coronary obstruction. Conclusion We suggest the use of Heart Rate Variability Analysis in linear and nonlinear domains, for prognostic purposes in patients with stable angina pectoris, in view of their overall impairment.

Evolutionary methods for self-organizing cooperation in peer-to-peer networks

The Peer-to-Peer network paradigm is drawing the attention of both final users and researchers for its features. P2P networks shift from the classic client-server approach to a high level of decentralization where there is no central control and all the nodes should be able not only to require services, but to provide them to other peers as well. While on one hand such high level of decentralization might lead to interesting properties like scalability and fault tolerance, on the other hand it implies many new problems to deal with. A key feature of many P2P systems is openness, meaning that everybody is potentially able to join a network with no need for subscription or payment systems. The combination of openness and lack of central control makes it feasible for a user to free-ride, that is to increase its own benefit by using services without allocating resources to satisfy other peers’ requests. One of the main goals when designing a P2P system is therefore to achieve cooperation between users. Given the nature of P2P systems based on simple local interactions of many peers having partial knowledge of the whole system, an interesting way to achieve desired properties on a system scale might consist in obtaining them as emergent properties of the many interactions occurring at local node level. Two methods are typically used to face the problem of cooperation in P2P networks: 1) engineering emergent properties when designing the protocol; 2) study the system as a game and apply Game Theory techniques, especially to find Nash Equilibria in the game and to reach them making the system stable against possible deviant behaviors. In this work we present an evolutionary framework to enforce cooperative behaviour in P2P networks that is alternative to both the methods mentioned above. Our approach is based on an evolutionary algorithm inspired by computational sociology and evolutionary game theory, consisting in having each peer periodically trying to copy another peer which is performing better. The proposed algorithms, called SLAC and SLACER, draw inspiration from tag systems originated in computational sociology, the main idea behind the algorithm consists in having low performance nodes copying high performance ones. The algorithm is run locally by every node and leads to an evolution of the network both from the topology and from the nodes’ strategy point of view. Initial tests with a simple Prisoners’ Dilemma application show how SLAC is able to bring the network to a state of high cooperation independently from the initial network conditions. Interesting results are obtained when studying the effect of cheating nodes on SLAC algorithm. In fact in some cases selfish nodes rationally exploiting the system for their own benefit can actually improve system performance from the cooperation formation point of view. The final step is to apply our results to more realistic scenarios. We put our efforts in studying and improving the BitTorrent protocol. BitTorrent was chosen not only for its popularity but because it has many points in common with SLAC and SLACER algorithms, ranging from the game theoretical inspiration (tit-for-tat-like mechanism) to the swarms topology. We discovered fairness, meant as ratio between uploaded and downloaded data, to be a weakness of the original BitTorrent protocol and we drew inspiration from the knowledge of cooperation formation and maintenance mechanism derived from the development and analysis of SLAC and SLACER, to improve fairness and tackle freeriding and cheating in BitTorrent. We produced an extension of BitTorrent called BitFair that has been evaluated through simulation and has shown the abilities of enforcing fairness and tackling free-riding and cheating nodes.

Stable isotope investigations of atmospheric nitrous oxide

ZusammenfassungDie Analyse von Isotopenverhältnissen ist von wachsender Bedeutung bei der Untersuchung von Quellen, Senken und chemischen Reaktionswegen atmosphärischer Spurengase. Distickstoffoxid (N2O) hat vier isotopisch einfach substituierte Spezies: 14N15N16O, 15N14N16O, 14N217O und 14N218O. In der vorliegenden Arbeit wurden massenspektrometrische Methoden entwickelt, die eine komplette Charakterisierung der Variationen im Vorkommen dieser Spezies ermöglichen. Es wird die bisher umfassendste Darstellung dieser Variationen in Troposphäre und Stratosphäre gegeben und mit Bezug auf eine Reihe von Laborexperimenten detailliert interpretiert.Die Laborexperimente machen einen großen Anteil dieser Doktorarbeit aus und konzentrieren sich auf die Isotopenfraktionierung in den stratosphärischen N2O-Senken, d. h. Photolyse und Reaktion mit elektronisch angeregten Sauerstoffatomen, O(1D). Diese Prozesse sind von dominantem Einfluß auf die Isotopenzusammensetzung von atmosphärischem N2O. Potentiell wichtige Parameter wie Temperatur- und Druckvariationen, aber auch Veränderungen der Wellenlänge im Fall der Photolyse wurden berücksichtigt. Photolyse bei stratosphärisch relevanten Wellenlängen > 190 nm zeigte immer Anreicherungen von 15N in beiden Stickstoffatomen des verbleibenden N2O wie auch in 17O und 18O. Die Anreicherungen waren am mittelständigen N-Atom signifikant höher als am endständigen N (mit mittleren Werten für 18O) und stiegen zu größeren Wellenlängen und niedrigeren Temperaturen hin an. Erstmalig wurden für 18O und 15N am endständigen N-Atom Isotopenabreicherungen bei 185 nm-Photolyse festgestellt. Im Gegensatz zur Photolyse waren die Isotopenanreicherungen bei der zweiten wichtigen N2O-Senke, Reaktion mit O(1D) vergleichsweise gering. Jedoch war das positionsabhängige Fraktionierungsmuster dem der Photolyse direkt entgegengesetzt und zeigte größere Anreicherungen am endständigen N-Atom. Demgemäß führen beiden Senkenprozesse zu charakteristischen Isotopensignaturen in stratosphärischem N2O. Weitere N2O-Photolyseexperimente zeigten, daß 15N216O in der Atmosphäre höchstwahrscheinlich mit der statistisch zu erwartenden Häufigkeit vorkommt.Kleine stratosphärische Proben erforderten die Anpassung der massenspektrometrischen Methoden an Permanentflußtechniken, die auch für Messungen an Firnluftproben von zwei antarktischen Stationen verwendet wurden. Das 'Firnluftarchiv' erlaubte es, den gegenwärtigen Trend und die präindustriellen Werte der troposphärischen N2O-Isotopensignatur zu bestimmen. Ein daraus konstruiertes globales N2O-Isotopenbudget ist im Einklang mit den besten Schätzungen der Gesamt-N2O-Emissionen aus Böden und Ozeanen.17O-Messungen bestätigten die Sauerstoffisotopenanomalie in atmosphärischem N2O, zeigten aber auch, daß N2O-Photolyse die Sauerstoffisotope gemäß einem massenabhängigen Fraktionierungsgesetz anreichert. Eine troposphärische Ursache für einen Teil des Exzeß-17O wurde vorgeschlagen, basierend auf der Reaktion von NH2 mit NO2, wodurch die Sauerstoffisotopenanomalie von O3 über NO2 an N2O übertragen wird.