Lipid transfers to HDL are predictors of precocious clinical coronary heart disease

Background: High-density-lipoprotein (HDL) has several antiatherogenic properties and, although the concentration of HDL-cholesterol negatively correlates with incidence of coronary artery disease (CAD), this is not sufficient to evaluate the overall HDL protective role. The aim was to investigate whether precocious CAD patients show abnormalities in lipid transfers to HDL, a fundamental step in HDL metabolism and function. Methods: Thirty normocholesterolemic CAD patients aged <50 y and 30 controls paired for sex, age and B.M.I. were studied. Fasting blood samples were collected for the in vitro lipid transfer assay and plasma lipid determination. A donor nanoemulsion labeled with radioactive free-cholesterol. cholesteryl esters, phospholipids and triglycerides was incubated with whole plasma and after chemical precipitation of non-HDL fractions, supernatant was counted for radioactivity in HDL. Results: LDL and HDL-cholesterol and triglycerides were equal in both groups. Transfers of free-cholesterol (3.8 +/- 1.2%vs 7.0 +/- 33%,p<0.0001) and triglycerides (3.7 +/- 1.7%vs 4.9 +/- 1.9%, p = 0.0125) were diminished in CAD patients whereas cholesteryl ester transfer increased (6.5 +/- 1.9%vs 4.8 +/- 1.8%, p = 0.0008); phospholipid transfer was equal (17.8 +/- 3.5% vs19.5 +/- 3.9%). Conclusion: Alterations in the transfer of lipids to HDL may constitute a new marker for precocious CAD and relation of this metabolic alteration with HDL antiatherogenic function should be investigated in future studies. (C) 2011 Published by Elsevier B.V.

Factors associated with maternal intrapartum transfers from a freestanding birth centre in Sao Paulo, Brazil: A case control study

Objectives: to identify factors associated with maternal intrapartum transfer from a freestanding birth centre to hospital. Design: case-control study with retrospective data collection. Participants and settings: cases included all 111 women transferred from a freestanding birth centre in Sao Paulo to the referral hospital, from March 2002 to December 2009. The controls were 456 women who gave birth in the birth centre during the same period who were not transferred, randomly selected with four controls for each case. Methods: data were obtained from maternal records. Factors associated with maternal intrapartum transfers were initially analysed using a chi(2) test of association. Variables with p < 0.20 were then included in multivariate analyses. A multiple logistic regression model was built using stepwise forward selection; variables which reached statistical significance at p < 0.05 were considered to be independently associated with maternal transfer. Findings: during the study data collection period, 111(4%) of 2,736 women admitted to the centre were transferred intrapartum. Variables identified as independently associated factors for intrapartum transfer included nulliparity (OR 5.1, 95% CI 2.7-9.8), maternal age >= 35 years (OR 5.4, 95% CI 2.1-13.4), not having a partner (OR 2.8, 95% CI 1.5-5.3), cervical dilation <= 3 cm on admission to the birth centre (OR 1.9, 95% CI 1.1-3.2) and between 5 and 12 antenatal appointments at the birth centre (OR 3.8, 95% CI 1.9-7.5). In contrast, a low correlation between fundal height and pregnancy gestation (OR 0.3, 95% CI 0.2-0.6) appeared to be protective against transfer. Conclusions and implications for practice: identifying factors associated with maternal intrapartum transfer could support decision making by women considering options for place of birth, and support the content of appropriate information about criteria for admission to a birth centre. Findings add to the evidence base to support identification of women in early labour who may experience later complications and could support timely implementation of appropriate interventions associated with reducing transfer rates. (C) 2012 Elsevier Ltd. All rights reserved.

Endosymbiosis in trypanosomatids: the genomic cooperation between bacterium and host in the synthesis of essential amino acids is heavily influenced by multiple horizontal gene transfers

Background Trypanosomatids of the genera Angomonas and Strigomonas live in a mutualistic association characterized by extensive metabolic cooperation with obligate endosymbiotic Betaproteobacteria. However, the role played by the symbiont has been more guessed by indirect means than evidenced. Symbiont-harboring trypanosomatids, in contrast to their counterparts lacking symbionts, exhibit lower nutritional requirements and are autotrophic for essential amino acids. To evidence the symbiont’s contributions to this autotrophy, entire genomes of symbionts and trypanosomatids with and without symbionts were sequenced here. Results Analyses of the essential amino acid pathways revealed that most biosynthetic routes are in the symbiont genome. By contrast, the host trypanosomatid genome contains fewer genes, about half of which originated from different bacterial groups, perhaps only one of which (ornithine cyclodeaminase, EC:4.3.1.12) derived from the symbiont. Nutritional, enzymatic, and genomic data were jointly analyzed to construct an integrated view of essential amino acid metabolism in symbiont-harboring trypanosomatids. This comprehensive analysis showed perfect concordance among all these data, and revealed that the symbiont contains genes for enzymes that complete essential biosynthetic routes for the host amino acid production, thus explaining the low requirement for these elements in symbiont-harboring trypanosomatids. Phylogenetic analyses show that the cooperation between symbionts and their hosts is complemented by multiple horizontal gene transfers, from bacterial lineages to trypanosomatids, that occurred several times in the course of their evolution. Transfers occur preferentially in parts of the pathways that are missing from other eukaryotes. Conclusion We have herein uncovered the genetic and evolutionary bases of essential amino acid biosynthesis in several trypanosomatids with and without endosymbionts, explaining and complementing decades of experimental results. We uncovered the remarkable plasticity in essential amino acid biosynthesis pathway evolution in these protozoans, demonstrating heavy influence of horizontal gene transfer events, from Bacteria to trypanosomatid nuclei, in the evolution of these pathways.

Optimization of Large-Scale Hydrothermal System Operation

This paper presents the development of a mathematical model to optimize the management and operation of the Brazilian hydrothermal system. The system consists of a large set of individual hydropower plants and a set of aggregated thermal plants. The energy generated in the system is interconnected by a transmission network so it can be transmitted to centers of consumption throughout the country. The optimization model offered is capable of handling different types of constraints, such as interbasin water transfers, water supply for various purposes, and environmental requirements. Its overall objective is to produce energy to meet the country's demand at a minimum cost. Called HIDROTERM, the model integrates a database with basic hydrological and technical information to run the optimization model, and provides an interface to manage the input and output data. The optimization model uses the General Algebraic Modeling System (GAMS) package and can invoke different linear as well as nonlinear programming solvers. The optimization model was applied to the Brazilian hydrothermal system, one of the largest in the world. The system is divided into four subsystems with 127 active hydropower plants. Preliminary results under different scenarios of inflow, demand, and installed capacity demonstrate the efficiency and utility of the model. From this and other case studies in Brazil, the results indicate that the methodology developed is suitable to different applications, such as planning operation, capacity expansion, and operational rule studies, and trade-off analysis among multiple water users. DOI: 10.1061/(ASCE)WR.1943-5452.0000149. (C) 2012 American Society of Civil Engineers.

RESULTS OF ULNAR NERVE NEUROTIZATION TO BICEPS BRACHII MUSCLE IN BRACHIAL PLEXUS INJURY

Objective: To evaluate the factors influencing the results of ulnar nerve neurotization at the motor branch of the brachii biceps muscle, aiming at the restoration of elbow flexion in patients with brachial plexus injury. Methods: 19 patients, with 18 men and 1 woman, mean age 28.7 years. Eight patients had injury to roots C5-C6 and 11, to roots C5-C6-C7. The average time interval between injury and surgery was 7.5 months. Four patients had cervical fractures associated with brachial plexus injury. The postoperative follow-up was 15.7 months. Results: Eight patients recovered elbow flexion strength MRC grade 4; two, MRC grade 3 and nine, MRC <3. There was no impairment of the previous ulnar nerve function. Conclusion: The surgical results of ulnar nerve neurotization at the motor branch of brachii biceps muscle are dependent on the interval between brachial plexus injury and surgical treatment, the presence of associated fractures of the cervical spine and occipital condyle, residual function of the C8-T1 roots after the injury and the involvement of the C7 root. Signs of reinnervation manifested up to 3 months after surgery showed better results in the long term. Level of Evidence: IV, Case Series.

Lipid Transfer to HDL is Higher in Marathon Runners than in Sedentary Subjects, but is Acutely Inhibited During the Run

Although exercise increases HDL-cholesterol, exercise-induced changes in HDL metabolism have been little explored. Lipid transfer to HDL is essential for HDL's role in reverse cholesterol transport. We investigated the effects of acute exhaustive exercise on lipid transfer to HDL. We compared plasma lipid, apolipoprotein and cytokine levels and in vitro transfer of four lipids from a radioactively labeled lipid donor nanoemulsion to HDL in sedentary individuals (n = 28) and in marathon runners (n = 14) at baseline, immediately after and 72 h after a marathon. While HDL-cholesterol concentrations and apo A1 levels were higher in marathon runners, LDL-cholesterol, apo B and triacylglycerol levels were similar in both groups. Transfers of non-esterified cholesterol [6.8 (5.7-7.2) vs. 5.2 (4.5-6), p = 0.001], phospholipids [21.7 (20.4-22.2) vs. 8.2 (7.7-8.9), p = 0.0001] and triacylglycerol [3.7 (3.1-4) vs. 1.3 (0.8-1.7), p = 0.0001] were higher in marathon runners, but esterified-cholesterol transfer was similar. Immediately after the marathon, LDL- and HDL-cholesterol concentrations and apo A1 levels were unchanged, but apo B and triacylglycerol levels increased. Lipid transfer of non-esterified cholesterol [6.8 (5.7-7.2) vs. 5.8 (4.9-6.6), p = 0.0001], phospholipids [21.7 (20.4-22.2) vs. 19.1 (18.6-19.3), p = 0.0001], esterified-cholesterol [3.2 (2.2-3.8) vs. 2.3 (2-2.9), p = 0.02] and triacylglycerol [3.7 (3.1-4) vs. 2.6 (2.1-2.8), p = 0.0001] to HDL were all reduced immediately after the marathon but returned to baseline 72 h later. Running a marathon increased IL-6 and TNF-alpha levels, but after 72 h these values returned to baseline. Lipid transfer, except esterified-cholesterol transfer, was higher in marathon runners than in sedentary individuals, but the marathon itself acutely inhibited lipid transfer. In light of these novel observations, further study is required to clarify how these metabolic changes can influence HDL composition and anti-atherogenic function.

Motor function measure scale, steroid therapy and patients with Duchenne muscular dystrophy

Objective: To assess the evolution of motor function in patients with Duchenne muscular dystrophy (DMD) treated with steroids (prednisolone or deflazacort) through the Motor Function Measure (MFM), which evaluates three dimensions of motor performance (D1, D2, D3). Methods: Thirty-three patients with DMD (22 ambulant, 6 non-ambulant and 5 who lost the capacity to walk during the period of the study) were assessed using the MFM scale six times over a period of 18 months. Results: All the motor functions remained stable for 14 months in all patients, except D1 for those who lost their walking ability. In ambulant patients, D2 (axial and proximal motor capacities) motor functions improved during six months; an improvement in D3 (distal motor capacity) was noted during the total follow-up. D1 (standing posture and transfers) and total score were useful to predict the loss of the ability to walk. Conclusions: The use of the MFM in DMD patients confirms the benefits of the steroid treatment for slowing the progression of the disease.

Demography and evolution of regional inequality

This paper addresses the importance of life cycle aspects in explaining the evolution of regional income inequality. The analysis of household microdata organized in age cohorts shows that Brazilian regional income inequality has different dynamics across generations, with income convergence being observed only for the older generations. The larger income share of younger generations produces a low speed of convergence in the country. When retirement payments, pensions, and other government transfers are excluded from income, convergence is not observed even for the older generations.

Upper Brachial Plexus Injuries: Grafts vs Ulnar Fascicle Transfer to Restore Biceps Muscle Function

BACKGROUND: Nerve transfers or graft repairs in upper brachial plexus palsies are 2 available options for elbow flexion recovery. OBJECTIVE: To assess outcomes of biceps muscle strength when treated either by grafts or nerve transfer. METHODS: A standard supraclavicular approach was performed in all patients. When roots were available, grafts were used directed to proximal targets. Otherwise, a distal ulnar nerve fascicle was transferred to the biceps branch. Elbow flexion strength was measured with a dynamometer, and an index comparing the healthy arm and the operated-on side was developed. Statistical analysis to compare both techniques was performed. RESULTS: Thirty-five patients (34 men) were included in this series. Mean age was 28.7 years (standard deviation, 8.7). Twenty-two patients (62.8%) presented with a C5-C6 injury, whereas 13 patients (37.2%) had a C5-C6-C7 lesion. Seventeen patients received reconstruction with grafts, and 18 patients were treated with a nerve transfer from the ulnar nerve to the biceps. The trauma to surgery interval (mean, 7.6 months in both groups), strength in the healthy arm, and follow-up duration were not statistically different. On the British Medical Research Council muscle strength scale, 8 of 17 (47%) patients with a graft achieved >= M3 biceps flexion postoperatively, vs 16 of 18 (88%) post nerve transfers (P = .024). This difference persisted when a muscle strength index assessing improvement relative to the healthy limb was used (P = .031). CONCLUSION: The results obtained from ulnar nerve fascicle transfer to the biceps branch were superior to those achieved through reconstruction with grafts.

On the Deactivation Mechanisms of Adenine-Thymine Base Pair

In this contribution, the multiconfigurational second-order perturbation theory method based on a complete active space reference wave function (CASSCF/CASPT2) is applied to study all possible single and double proton/hydrogen transfers between the nucleobases in the adenine-thymine (AT) base pair, analyzing the role of excited states with different nature [localized (LE) and charge transfer (CT)] and considering concerted as well as step-wise mechanisms. According to the findings, once the lowest excited states, localized in adenine, are populated during UV irradiation of the Watson-Crick base pair, the proton transfer in the N-O bridge does not require high energy in order to populate a CT state. The latter state will immediately relax toward a crossing with the ground state, which will funnel the system to either the canonical structure or the imino-enol tautomer. The base pair is also capable of repairing itself easily since the imino-enol species is unstable to thermal conversion.

Assessment of Pharmaceutical Equivalence: Difference Test or Equivalence Test?

Pharmaceutical equivalence is an important step towards the confirmation of similarity and Interchangeability among pharmaceutical products, particularly regarding those that win not be tested for bioequivalence. The aim of this paper is to compare traditional difference testing to two one-side equivalence tests in the assessment of pharmaceutical equivalence, by means of equivalence studies between similar, generic and reference products of acyclovir cream, atropine sulfate injection, meropenem for injection, and metronidazole injection. All tests were performed in accordance with the Brazilian Pharmacopeia or the United States Pharmacopeia. All four possible combinations of results arise in these comparisons of difference testing and equivalence testing. Most of the former did not show significant difference, whereas the latter presented similarity. We concluded that equivalence testing is more appropriate than difference testing, what can make it a useful tool to assess pharmaceutical equivalence in products that will not be tested for bioequivalence.

Removal from the plasma of the free and esterified forms of cholesterol and transfer of lipids to HDL in type 2 diabetes mellitus patients

Background: The aim was to investigate new markers for type 2 diabetes (T2DM) dyslipidemia related with LDL and HDL metabolism. Removal from plasma of free and esterified cholesterol transported in LDL and the transfer of lipids to HDL are important aspects of the lipoprotein intravascular metabolism. The plasma kinetics (fractional clearance rate, FCR) and transfers of lipids to HDL were explored in T2DM patients and controls, using as tool a nanoemulsion that mimics LDL lipid structure (LDE). Results: C-14- cholesteryl ester FCR of the nanoemulsion was greater in T2DM than in controls (0.07 +/- 0.02 vs. 0.05 +/- 0.01 h(-1), p = 0.02) indicating that LDE was removed faster, but FCR H-3- cholesterol was equal in both groups. Esterification rates of LDE free-cholesterol were equal. Cholesteryl ester and triglyceride transfer from LDE to HDL was greater in T2DM (4.2 +/- 0.8 vs. 3.5 +/- 0.7%, p = 0.03 and 6.8 +/- 1.6% vs. 5.0 +/- 1.1, p = 0.03, respectively). Phospholipid and free cholesterol transfers were not different. Conclusions: The kinetics of free and esterified cholesterol tended to be independent in T2DM patients and the lipid transfers to HDL were also disturbed. These novel findings may be related with pathophysiological mechanisms of diabetic macrovascular disease.

Multiple invasions of Gypsy and Micropia retroelements in genus Zaprionus and melanogaster subgroup of the genus Drosophila

Abstract Background The Zaprionus genus shares evolutionary features with the melanogaster subgroup, such as space and time of origin. Although little information about the transposable element content in the Zaprionus genus had been accumulated, some of their elements appear to be more closely related with those of the melanogaster subgroup, indicating that these two groups of species were involved in horizontal transfer events during their evolution. Among these elements, the Gypsy and the Micropia retroelements were chosen for screening in seven species of the two Zaprionus subgenera, Anaprionus and Zaprionus. Results Screening allowed the identification of diverse Gypsy and Micropia retroelements only in species of the Zaprionus subgenus, showing that they are transcriptionally active in the sampled species. The sequences of each retroelement were closely related to those of the melanogaster species subgroup, and the most parsimonious hypothesis would be that 15 horizontal transfer events shaped their evolution. The Gypsy retroelement of the melanogaster subgroup probably invaded the Zaprionus genomes about 11 MYA. In contrast, the Micropia retroelement may have been introduced into the Zaprionus subgenus and the melanogaster subgroup from an unknown donor more recently (~3 MYA). Conclusion Gypsy and Micropia of Zaprionus and melanogaster species share similar evolutionary patterns. The sharing of evolutionary, ecological and ethological features probably allowed these species to pass through a permissive period of transposable element invasion, explaining the proposed waves of horizontal transfers.

The uncertain consequences of transferring bacterial strains between laboratories - rpoS instability as an example

Abstract Background Microbiological studies frequently involve exchanges of strains between laboratories and/or stock centers. The integrity of exchanged strains is vital for archival reasons and to ensure reproducible experimental results. For at least 50 years, one of the most common means of shipping bacteria was by inoculating bacterial samples in agar stabs. Long-term cultures in stabs exhibit genetic instabilities and one common instability is in rpoS. The sigma factor RpoS accumulates in response to several stresses and in the stationary phase. One consequence of RpoS accumulation is the competition with the vegetative sigma factor σ70. Under nutrient limiting conditions mutations in rpoS or in genes that regulate its expression tend to accumulate. Here, we investigate whether short-term storage and mailing of cultures in stabs results in genetic heterogeneity. Results We found that samples of the E. coli K-12 strain MC4100TF exchanged on three separate occasions by mail between our laboratories became heterogeneous. Reconstruction studies indicated that LB-stabs exhibited mutations previously found in GASP studies in stationary phase LB broth. At least 40% of reconstructed stocks and an equivalent proportion of actually mailed stock contained these mutations. Mutants with low RpoS levels emerged within 7 days of incubation in the stabs. Sequence analysis of ten of these segregants revealed that they harboured each of three different rpoS mutations. These mutants displayed the classical phenotypes of bacteria lacking rpoS. The genetic stability of MC4100TF was also tested in filter disks embedded in glycerol. Under these conditions, GASP mutants emerge only after a 3-week period. We also confirm that the intrinsic high RpoS level in MC4100TF is mainly due to the presence of an IS1 insertion in rssB. Conclusions Given that many E. coli strains contain high RpoS levels similar to MC4100TF, the integrity of such strains during transfers and storage is questionable. Variations in important collections may be due to storage-transfer related issues. These results raise important questions on the integrity of bacterial archives and transferred strains, explain variation like in the ECOR collection between laboratories and indicate a need for the development of better methods of strain transfer.

Fragmentação geopolítica: uma análise estrutural das propostas de separatismo no Brasil

Este trabalho tem por objetivo dar luz ao debate sobre a criação dos novos entes federativos, trazendo elementos objetivos sobre a caracterização socioeconômica dos novos espaços geopolíticos e seus respectivos papéis no novo contexto espacial do sistema inter-regional brasileiro. O artigo traz resultados inéditos para a discussão, buscando, inicialmente, identificar padrões hierárquicos e de dependência espacial e produtiva neste novo contexto federativo. Tais resultados subsidiama analise subsequente dos impactos da nova configuração das transferências constitucionais, que identifica pormeio de simulações comummodelo inter-regional de insumo-produto especialmente calibrado para as 33 regiões consideradas no estudo, não apenas os potenciais ganhadores e perdedores, mas também os mecanismos de interação espacial subjacentes a estes processos.