Quantitation of drugs via molecularly imprinted polymer solid phase extraction and electrospray ionization mass spectrometry: benzodiazepines in human plasma

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)The association of solid phase extraction with molecularly imprinted polymers (MIP) and electrospray ionization mass spectrometry (ESI-MS) is applied to the direct extraction and quantitation of benzodiazepines in human plasma. The target analytes are sequestered by MIP and directly analyzed by ESI-MS. Due to the MIP highly selective extraction, ionic suppression during ESI is minimized; hence no separation is necessary prior to ESI-MS, which greatly increases analytical speed. Benzodiazepines (medazepam, nitrazepam, diazepam, chlordiazepoxide, clonazepam and midazolam) in human plasma were chosen as a proof-of-principle case of drug analyses by MIP-ESI-MS in a complex matrix. MIP-ESI-MS displayed good figures of merits for medazepam, nitrazepam, diazepam, chlordiazepoxide and midazolam, with analytical calibration curves ranging from 10 to 250 mu g L(-1) (r > 0.98) with limit of quantification <10 mu g L(-1) and acceptable within-day and between-day precision and accuracy.1361837533757Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Ministerio de Ciencia e Tecnologia (INOMAT)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundacao de Amparo a Pesquisa do Estado de Minas Gerais (FAPEMIG, Belo Horizonte, Brazil) [CDS-APQ-01323-09, CDS-APQ-01612-10

Efficacy of diadynamic currents as an adjunct to exercise to manage symptoms of knee osteoarthritis in adults: A randomized controlled clinical trial

Objective To investigate the effect of diadynamic currents administered prior to exercises on pain and disability in patients with osteoarthritis of the knee. Design A randomized-controlled trial. Setting Special Rehabilitation Services in Taboão da Serra. Participants Patients with bilateral knee osteoarthritis. Intervention Participants were randomly allocated to Group I (diadynamic currents and exercises; n = 30, 60 knees) or Group II (exercises alone; n = 30, 60 knees) and were treated three times a week for 8 weeks. Main outcome measures The primary outcome measures were change in knee pain evaluated by visual analog scale and disability Index Score (Lequesne). Secondary outcomes included change in mobility (Timed Up and Go test), range of motion (goniometer), muscle strength (dynamometer), a composite score for pain and disability (Western Ontario and McMaster Universities Osteoarthritis questionnaire), and a drug diary to measure consumption of rescue pain medication (paracetamol). All measurements were collected at baseline, 8 weeks, and 6 months from baseline (follow-up). Results There were 60 participants with a mean (SD) age of 63.40 (8.20) years. Between-group differences in the follow-up (8 weeks and 6 months) were observed for pain at rest, pain during activities of daily living and disability. There was improvement in Group I that was maintained for the three variables 6 months after treatment. Mean difference for pain at rest was −3.08 points (95% confidence interval −4.13; −2.02), p < 0.01 with an effect size of 1.4; mean difference for pain during activities of daily living was −2.40 points (95% confidence interval −3.34; −1.45), p < 0.01 with an effect size of 1.24; and mean difference for disability was −4.08 points (95% confidence interval −5.89; −2.26), p < 0.01 with an effect size of 1.04. Conclusion Patients with symptomatic knee osteoarthritis receiving 8 weeks of treatment with diadynamic currents as an adjunct to a program of exercises had significantly greater improvements in pain and disability than those receiving exercises alone. Beneficial effects were sustained for 6 months

The BINGO Project: III. Optical design and optimization of the focal plane

Context. The Baryon Acoustic Oscillations from Integrated Neutral Gas Observations (BINGO) telescope was designed to measure the fluctuations of the 21 cm radiation arising from the hyperfine transition of neutral hydrogen. It is also aimed at measuring the baryon acoustic oscillations (BAO) from such fluctuations, thereby serving as a pathfinder to future, deeper intensity mapping surveys. The requirements for the Phase 1 of the projects consider a large reflector system (two 40 m-class dishes in a crossed-Dragone configuration) illuminating a focal plane with 28 horns to measure the sky, with two circular polarizations in a drift scan mode to produce measurements of the radiation in intensity (I) as well as the circular (V) polarization. Aims. In this paper, we present the optical design for the instrument. We describe the optical arrangement of the horns in the focal plane to produce a homogeneous and well-sampled map after the end of Phase 1, as well as the intensity and polarization properties of the beams. Our analysis provides an optimal model for the location of the horns in the focal plane, producing a homogeneous and Nyquist-sampled map after the nominal survey time. Methods. We used the GRASP package to model the focal plane arrangement and performed several optimization tasks to arrive at the current configuration, including an estimation of the sidelobes corresponding to the diffraction patterns of the two mirrors. The final model for the focal plane was defined through a combination of neural network and other direct optimization methods. Results. We arrived at an optimal configuration for the optical system that includes the focal plane positioning and the beam behavior of the instrument. We present an estimate of the expected sidelobes both for intensity and polarization, as well as the effect of band averaging on the final sidelobes, as well as an estimation of the cross-polarization leakage for the final configuration. Conclusions. We conclude that the chosen optical design meets the requirements for the project in terms of polarization purity and area coverage as well as a homogeneity of coverage so that BINGO can perform a successful BAO experiment. We further conclude that the requirements on the placement and rms error on the mirrors are also achievable so that a successful experiment can be conducted

The BINGO project: I. Baryon acoustic oscillations from integrated neutral gas observations

Context. Observations of the redshifted 21-cm line of neutral hydrogen (HI) are a new and powerful window of observation that offers us the possibility to map the spatial distribution of cosmic HI and learn about cosmology. Baryon Acoustic Oscillations from Integrated Neutral Gas Observations (BINGO) is a new unique radio telescope designed to be one of the first to probe baryon acoustic oscillations (BAO) at radio frequencies. Aims. BINGO has two science goals: cosmology and astrophysics. Cosmology is the main science goal and the driver for BINGO's design and strategy. The key of BINGO is to detect the low redshift BAO to put strong constraints on the dark sector models and test the ICDM (cold dark matter) model. Given the versatility of the BINGO telescope, a secondary goal is astrophysics, where BINGO can help discover and study fast radio bursts (FRB) and other transients, as well as study Galactic and extragalactic science. In this paper, we introduce the latest progress of the BINGO project, its science goals, describing the scientific potential of the project for each goal and the new developments obtained by the collaboration. Methods. BINGO is a single dish transit telescope that will measure the BAO at low-z by making a 3D map of the HI distribution through the technique of intensity mapping over a large area of the sky. In order to achieve the project's goals, a science strategy and a specific pipeline for cleaning and analyzing the produced maps and mock maps was developed by the BINGO team, which we generally summarize here. Results. We introduce the BINGO project and its science goals and give a general summary of recent developments in construction, science potential, and pipeline development obtained by the BINGO Collaboration in the past few years. We show that BINGO will be able to obtain competitive constraints for the dark sector. It also has the potential to discover several FRBs in the southern hemisphere. The capacity of BINGO in obtaining information from 21-cm is also tested in the pipeline introduced here. Following these developments, the construction and observational strategies of BINGO have been defined. Conclusions. There is still no measurement of the BAO in radio, and studying cosmology in this new window of observations is one of the most promising advances in the field. The BINGO project is a radio telescope that has the goal to be one of the first to perform this measurement and it is currently being built in the northeast of Brazil. This paper is the first of a series of papers that describe in detail each part of the development of the BINGO project

Otodental syndrome

The otodental syndrome also named otodental dysplasia, is characterised by a striking dental phenotype known as globodontia, associated with sensorineural high frequency hearing loss and eye coloboma. Globodontia occurs in both primary and permanent dentition, affecting canine and molar teeth (i.e. enlarged bulbous malformed posterior teeth with almost no discernable cusps or grooves). The condition appears to be inherited in an autosomal dominant mode, although sporadic cases have been reported. It is a rare disease, a few families have been described in the literature. In the British family, the locus for oculo-oto-dental syndrome was mapped to 20q13.1 within a 12-cM critical chromosomal region. Dental management is complex, interdisciplinary and will include regular follow up, scheduled teeth extraction and orthodontic treatment. Hearing checks and, if necessary, hearing aids are mandatory, as well as eye examination and ad hoc treatment if necessary

Evolutionary connectionism: algorithmic principles underlying the evolution of biological organisation in evo-devo, evo-eco and evolutionary transitions

The mechanisms of variation, selection and inheritance, on which evolution by natural selection depends, are not fixed over evolutionary time. Current evolutionary biology is increasingly focussed on understanding how the evolution of developmental organisations modifies the distribution of phenotypic variation, the evolution of ecological relationships modifies the selective environment, and the evolution of reproductive relationships modifies the heritability of the evolutionary unit. The major transitions in evolution, in particular, involve radical changes in developmental, ecological and reproductive organisations that instantiate variation, selection and inheritance at a higher level of biological organisation. However, current evolutionary theory is poorly equipped to describe how these organisations change over evolutionary time and especially how that results in adaptive complexes at successive scales of organisation (the key problem is that evolution is self-referential, i.e. the products of evolution change the parameters of the evolutionary process). Here we first reinterpret the central open questions in these domains from a perspective that emphasises the common underlying themes. We then synthesise the findings from a developing body of work that is building a new theoretical approach to these questions by converting well-understood theory and results from models of cognitive learning. Specifically, connectionist models of memory and learning demonstrate how simple incremental mechanisms, adjusting the relationships between individually-simple components, can produce organisations that exhibit complex system-level behaviours and improve the adaptive capabilities of the system. We use the term “evolutionary connectionism” to recognise that, by functionally equivalent processes, natural selection acting on the relationships within and between evolutionary entities can result in organisations that produce complex system-level behaviours in evolutionary systems and modify the adaptive capabilities of natural selection over time. We review the evidence supporting the functional equivalences between the domains of learning and of evolution, and discuss the potential for this to resolve conceptual problems in our understanding of the evolution of developmental, ecological and reproductive organisations and, in particular, the major evolutionary transitions

No evidence for an association between the -36A>C phospholamban gene polymorphism and a worse prognosis in heart failure

Background: In Brazil, heart failure leads to approximately 25,000 deaths per year. Abnormal calcium handling is a hallmark of heart failure and changes in genes encoding for proteins involved in the re-uptake of calcium might harbor mutations leading to inherited cardiomyopathies. Phospholamban (PLN) plays a prime role in cardiac contractility and relaxation and mutations in the gene encoding PLN have been associated with dilated cardiomyopathy. In this study, our objective was to determine the presence of the -36A>C alteration in PLN gene in a Brazilian population of individuals with HF and to test whether this alteration is associated with heart failure or with a worse prognosis of patients with HF. Methods: We genotyped a cohort of 881 patients with HF and 1259 individuals from a cohort of individuals from the general population for the alteration -36A>C in the PLN gene. Allele and genotype frequencies were compared between groups (patients and control). In addition, frequencies or mean values of different phenotypes associated with cardiovascular disease were compared between genotypic groups. Finally, patients were prospectively followed-up for death incidence and genotypes for the -36A>C were compared regarding mortality incidence in HF patients. Results: No significant association was found between the study polymorphism and HF in our population. In addition, no association between PLN -36A>C polymorphism and demographic, clinical and functional characteristics and mortality incidence in this sample of HF patients was observed. Conclusion: Our data do not support a role for the PLN -36A>C alteration in modulating the heart failure phenotype, including its clinical course, in humans