Fundacao De Amparo A Pesquisa Do Estado De Sao Paulo Research Articles

Accuracy of a Simple Screening Tool (PALI-SP) to Predict Palliative Care Needing of In-Hospital Adult Patients in Five Tertiary Brazilian Hospitals

Background: To identify near of end-of-life in-hospital patients to provide them adequate support is a complex task. A simple and easily applicable tool is still needed. The aim of this study was to measure the accuracy of a simple tool with four questions, including two surprise questions, to predict one-year mortality of adult patients. Methods: This was a multicenter prospective observational cohort accomplishing five Brazilian public tertiary hospitals. A four questions tool (PALI-SP), able to classify patients in five categories was previously developed to help the coordination of care based on disease progression. This questionnaire was applied to the caring physician of each consecutively hospital admitted patient, during seven consecutive days. Data were collected between 2014 and 2015. A proportional hazard Cox model was used to the analysis. Results: A total of 1810 patients were studied. Patients’ age was 55±19 years-old, 833(46%) were females, 798(44%) were in a medical ward, and 1231(68%) have no advanced diseases. 975(54%) of analyses were done for physicians who had ≤ 3 years since graduation. The one-year mortality was 439(24%), death occurred within 27[9,111] days after the initial evaluation, non-survivors were younger, and have no-advanced diseases in 40% (174/439), followed by metastatic cancer [91/439(21%)]. The tool had the unadjusted and adjusted accuracies of 0.716(CI-95%=0.687-0.746) and 0.769(CI-95%=0.742-0.795) respectively. The five prognostic classification groups had incremental risk-ratios of one-year mortality: Group I = reference, Group II =1.484(0.885-2.487), Group IIIA=3.114(1.634–5.936), Group IIIB = 3.728(2.962–4.692), and Group IV = 6.339(4.618–8.702). Interpretation: This simple screening tool (PALI-SP) has a good overall accuracy to predict one-year mortality of in-hospital patients. Funding Statement: Study funded by the governmental agency Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP). Declaration of Interests: The authors have no conflict of interests to declare. Ethics Approval Statement: The study was approved by the local ethics committee of the Hospital das Clinicas de Sao Paulo under the process number 507007/07/2014. Informed consent was obtained from all patients and physicians prior to data collection. Trial Registration: The authors state that there is no Brazilian or US national clinical trials registration.

PRPS1 Gene Mutation Causes Complex X-Linked Adult-Onset Cerebellar Ataxia in Women.

Inherited retinal dystrophies (IRD) comprise a heterogeneous group of disorders that affect visual function. IRD occur in isolated forms or in association with systemic abnormalities.1 Over 300 disease-causing genes have been identified in IRD. The authors thank Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) for have funded this study.

Clinical Characteristics and Comorbidities of COVID-19 in Down Syndrome Individuals: First Year Report in Brazil

Background: Down Syndrome (DS) is one of the most impacted population to the COVID-19 pandemic.Methods: The markers for demographic profile, clinical symptoms, comorbidities, and the clinical of severe acute respiratory syndrome (SARS)evolution of first year of COVID-19 pandemic in Brazil was obtained from a Brazilian open-access database. The data were compared between (i) individuals with DS and positive for COVID-19 [G1; 1,619 (0.4%)] and individuals with SARS due to other etiologic agents [G2; 1,431 (0.4%)]; (ii) G1 individuals versus individuals with COVID-19, but without DS or comorbidities [G3; 222,181 (64.8%)].Findings: Individuals from G1 when compared to G2 were older (≥25 yo), presented more symptoms related to severe illness and comorbidities, needed more frequently intensive care unit (ICU) treatment as well as noninvasive mechanical ventilation (MV), and presented a nearly 3-fold-increased risk for mortality. Individuals from G1 when compared to G3 were younger (Interpretation: Individuals with DS are most affected by COVID-19 and demonstrated particularities regarding comorbidities, clinical signs and symptoms, needed MV regularly, and high mortality rate.Funding: MNB received a grant from FAPESP (Fundação de Amparo à Pesquisa do Estado de São Paulo – Acronym for São Paulo Research Foundation; #2021/05810-7).Declaration of Interest: None to declare.

Safety and Immunogenicity of CoronaVac in People Living with HIV

Background: People living with HIV (PLWH) may have a poor or delayed response to vaccines, mainly when CD4+ T cell counts are low. There are limited data concerning the safety and immunogenicity of COVID-19 vaccines in PLWH.Methods: This prospective controlled study evaluated the safety and immunogenicity of the SARS-CoV-2 inactivated vaccine CoronaVac in PLWH compared with controls with no known immunosuppression. Immunogenicity was assessed with SARS-CoV-2 IgG seroconversion (SC), neutralizing antibodies (NAb) activity, and factor increase in IgG geometric mean titers (FI-GMT). We also investigated if levels of CD4+ T cell counts (3) were associated with CoronaVac immunogenicity.Findings: 511 participants (215 PLWH and 296 controls) were eligible for the immunogenicity analysis. At vaccine completion (D69), although the percentage of participants with SC and NAb positivity was high for both PLWH and controls, it was somewhat lower in PLWH. CD4+ T cell was identified as a relevant factor for immunogenicity, with lower SC and NAb positivity in PLWH with CD4+ counts 3 compared to those with ≥500 cells/mm3. In a multivariable logistic regression model for NAb positivity after a complete two-dose regimen adjusted for age and sex, compared with PLWH with a CD4+ T cell count 3, those with CD4+ counts ≥500/mm3 had 2·26 times the odds of having positivity in NAb activity (95% CI 1·18-4·32; p=0·014), whereas controls had 3·21 times the odds of this outcome. No serious adverse reactions were reported during the study.Interpretation: Immunogenicity following CoronaVac in PLWH seems robust but reduced compared with controls; PLWH with CD4+ counts Funding: Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP); Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq); and B3 - Bolsa de Valores do Brasil.Declaration of Interest: EGK is the Principal Investigator for the CoronaVac phase 3 clinical trial at University of Sao Paulo. VIAS is the Principal Investigator for the Janssen COVID-19 vaccine phase 3 clinical trial at University of Sao Paulo. INCOMPLETE, MISSING SOME AUTHORS FROM DOIEthical Approval: The national and local ethics committees approved the study.

Treatment with methotrexate carried in lipid core nanoparticles prevents the development of diastolic dysfunction in septic rats

Abstract Introduction In the development of sepsis, besides the dysregulation of the immune system and disturbances of several vital organs, life-threatening cardiac dysfunction often occurs. Previously, we showed that non-protein nanoparticles that resemble the lipid structure of low-density lipoprotein, termed LDE, concentrate in inflammatory sites. When incorporated in LDE, the cellular uptake of MTX increases several-fold compared to the uptake of commercial MTX. The novel LDE-MTX formulation was shown to have the ability to modulate the immune response in in rabbits with atherosclerosis and in rats with myocardial infarction. LDE-MTX reduced the inflammation and improved the post-infarction cardiac function by increasing the release of angiogenesis, thereby improving hypoxia. The aim of the current study was to test the hypothesis whether LDE-MTX could also improve the cardiac status in septic rats. Methods Septicemia was induced in Wistar rats by two I.P. injections of lipopolysaccharide (LPS, 10mg/kg) administered with a 24h interval. Rats were allocated to control group (CT, without sepsis; n=5) and 3 groups with sepsis: LDE (n=7), treated with LDE only; MTX (n=6), with commercial MTX (1mg/kg); and LDE-MTX (n=7), with LDE-MTX (1mg/kg). Echocardiography was performed 72h after sepsis induction. Animals were euthanised and LV tissues were collected for protein expression analysis of inflammatory, apoptotic, angiogenesis, hypoxia and adenosine bioavailability markers. Results Septic rats treated with LDE developed diastolic dysfunction and presented decreased diastolic volume and diameter of the LV. Treatment with LDE-MTX totally prevented the appearance of diastolic dysfunction and the alterations in LV diastolic dilation. Also, LDE-MTX treatment elicited cardiac hypertrophy through the increase of the thickness of septum and of the LV posterior wall. LDE-MTX increased LV mass and the relative heart weight, as compared to the other 3 groups. There were no differences in the protein expression of inflammatory (lymphocytes, tumor necrosis factor, interleukins) and apoptotic (caspases and B-cell lymphoma family) markers among the four groups. However, LDE-MTX showed higher expression of CD68 (macrophage marker). Angiogenesis was higher, while cellular hypoxia was lower in LDE-MTX, respectively represented by vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1 alpha, in comparison to the other 3 groups. The intracellular adenosine bioavailability was increased in LDE-MTX-treated animals, as promoted by the higher expression of the A1 receptor, as compared to CT. Conclusion The treatment with LDE-MTX was successful in precluding the appearance of the cardiac dysfunction associated to sepsis. This outcome was conceivably attained by different effects of the treatment observed here, such as those on angiogenesis, macrophage recruitment and adenosine bioavailability in the LV. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): FAPESP (Fundacao de Amparo a Pesquisa do Estado de Sao Paulo)

Influence of resistance exercise training in diabetic hypertrophy renal: The role of mTOR and Acetyl CoA Carboxylase

Diabetic kidney disease (DKD) is a progressive complication that develops from diabetes. An important change observed is renal hypertrophy associated with the mTOR pathway. On the other hand, increasing evidence indicates that the reduction in the phosphorylation of Acetyl‐CoA Carboxylase (ACC) may be important in the development of Renal Fibrosis. Therefore, it is fundamental to understand non‐pharmacological intervention as the effect of resistance training (RET) to prevent these complications.In this study, our aim is evaluating the RET on the renal hypertrophy.Male Wistar rats were divided into 4 groups: control (C=8), control trained (CT=8), diabetic (D=8) and diabetic trained (DT=8). DM (glycaemia>250mg/dL) was induced by Streptozotocin (STZ) (50mg/kg, i.v.). Trained groups were submitted to a resistance exercise training protocol on Ladder climb (8wk). The expression of Akt/mTOR pathway was evaluated by two technical, western blotting and multiplex. Immunohistochemical was used to analyze the expression by ACC. A hypertrophy renal index was calculated by the reason the kidney weight/body weight. The histomorphology was analyzed by hematoxylin and eosin stain.RET improved renal parameters in the DT group showing a decreased proteinuria (DS:15±1.5; DT:16±2.0; CS:38±3; CT:16±2mg/24h). The renal expression of mTOR and Akt, was increased in the DS animals, and the early RET was able to prevent, the same results were observed in the hypertrophy renal index (p<0,05). The ACC was decreased in DS group and RET normalized this expression (p<0,05). Surprisingly, when analyzing the morphology was not find any difference between the groups.Our findings showed that RET was able to prevent renal hypertrophy, molecularly, and improvement of the renal parameters induced by experimental diabetes. These results demonstrate that the RET the clinical application in early diabetic patients may help prevent and/or treat the renal hypertrophy.Support or Funding InformationSources of Funding This study was supported by Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) and Conselho Nacional de Desenvolvimento Cientıfico e Tecnologico (CNPq).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Fungal Community Ecology Using MALDI-TOF MS Demands Curated Mass Spectral Databases.

Authors thank professors Marc-Andre Lachance and GregThorn for critical reading on initial drafts of this piece. Mariana Cereia, English teacher, kindly proofread the final version. Authors also thank Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP), Conselho de Desenvolvimento Cientifico e Tecnologico (CNPq) and National System for Research on Biodiversity (Sisbiota-Brazil, CNPq 563260/2010-6/FAPESP n◦ 2010/52322-3) for supporting previous work that led to this opinion piece. CS thanks the Universidad de La Frontera (Temuco, Chile) for the partial funding from Project DIUFRO DI18-0121. NL thanks the partial support by the Portuguese Foundation for Science and Technology (FCT), the strategic funding of the UID/BIO/04469/2019 unit, COMPETE 2020 (POCI-01-0145-FEDER-006684) and the BioTecNorte operation (NORTE-01-0145-FEDER-000004), funded by the European Regional Development Fund through Norte2020—Programa Operacional Regional do Norte.

EDUCAÇÃO SUPERIOR NO BRASIL E OS CONDICIONAMENTOS ÀS POLÍTICAS NACIONAIS

O artigo apresenta os resultados da pesquisa “A avaliação da educação superior no Brasil: sistema implementado pelo governo federal e uso dos seus resultados na gestão institucional”, financiado pela Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), com foco nos aspectos, reconhecidos pelos gestores acadêmicos, que dizem respeito aos efeitos da regulação transnacional nos processos avaliativos instituídos pelo Sistema Nacional de Avaliação da Educação Superior (Sinaes). Os procedimentos metodológicos apoiam-se em revisão de literatura, análise da legislação que disciplina a avaliação da educação superior, documentos governamentais, entrevistas com gestores acadêmicos e presidentes de Comissões Próprias de Avaliação (CPA) de instituições públicas e privadas. Os resultados apontam que as políticas de avaliação da educação superior brasileira incorporam recomendações e práticas da regulação transnacional, não se tratando ainda de apropriação direta, mas de sua reelaboração às condições institucionais nacionais, sem, contudo, uma percepção crítica sobre as exigências postas.

Perspectivas da Educação Não Escolar no Trato com Jovens Infratores

Resumo: O presente artigo é resultado do trabalho de pesquisa financiado pela FAPESP (Fundação de Amparo à Pesquisa do Estado de São Paulo) e foi desenvolvido no ano de 2014. A pesquisa tem por objetivo apresentar os limites e as contribuições da educação não escolar promovida por socioeducadores do Núcleo de Acolhimento Integrado de Sorocaba (NAIS), identificando os fundamentos e as perspectivas que orientam as práticas educativas, que foram averiguadas por meio de entrevistas semiestruturadas. Ao conhecer a realidade educacional vivida pelos jovens atendidos pelo NAIS, intenciona-se contribuir com a educação desenvolvida por essa instituição e, também, sinalizar alternativas que possam qualificar as ações educativas não escolares.

Role Of The NLRP3/Inflammasome On Aldosterone‐Induced Vascular Damage

Aldosterone (Aldo), a steroid with mineralocorticoid activity, is closely associated with vascular inflammation, remodeling and dysfunction. NLRP3/inflammasome, a member of cytoplasmic NOD‐like receptors, plays important role on inflammatory processes. We postulated that NLRP3/inflammasome mediates aldosterone‐induced vascular damage. To test this hypothesis we analyzed vascular structure and function and inflammatory profile of wild‐type (WT), NLRP3 knockout (NLRP3−/−) and Caspase‐1 knockout (Casp‐1−/−) mice treated with vehicle or Aldo (600 ug/kg/day for 14 days, via osmotic mini‐pump) while receiving 1% saline to drink. Aldo infusion did not change the final mean arterial pressure (WT: 101,9 ± 4,8 vs Aldo: 107,4 ± 5,1), but increased plasma levels of IL‐1β (WT: 588,0 ± 103 vs Aldo: 2333,9 ± 658,8* pg/mL, *P<0.05), as well as cleaved caspase‐1 and mature IL‐1β in the mesentery arteries, determined by ELISA and western blot, respectively, in WT mice. Apocynin (antioxidant agent) treatment prevented Aldo‐induced effects. NLRP3−/−and Casp‐1−/− mice were protected against Aldo‐induced vascular changes, i.e. they did not exhibit hypercontractility to phenylephrine [maximal effects (Emax) (WT: 75,2 ± 9,6 vs Aldo: 155,1 ± 22,1* % of KCl‐induced contractility, *P<0.05)] or reduced ACh‐induced relaxation upon Aldo treatment maximal effects [(Emax) (WT: 87,7 ± 2,1 vs Aldo: 34,2 ± 3,3*, % of relaxation, *P<0.05)]. Aldo infusion increased media:lumen ratio and media cross‐sectional area of resistance arteries, augmented RNA expression for inflammatory markers [(ICAM‐1 and VCAM‐1) 3 and 5‐folds, respectively] and the number of adhered macrophages in aortic segments. These Aldo‐induced changes were blunted in NLRP3−/−and Casp‐1−/− mice. To elucidate the role of NLRP3 in the vasculature, we performed bone marrow transplantation (BMT) from WT to NLRP3−/− mice (WTàNLRP3−/−), BMT chimeric mice were protected from Aldo‐induced vascular dysfunction and remodeling. All together these data suggest that NLRP3/inflammasome activation in the vasculature is oxidative stress‐dependent, and plays a crucial role on Aldo‐induced vascular dysfunction and remodeling.Support or Funding InformationFinancial Support: Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) e Coordenação de Aperfeiçoamento de Ensino Superior 88887.092495/2015‐00 (CAPES), Brazil.

A dinâmica do enriquecimento paulista no século XIX: das origens à diversificação do capital da família Lacerda Franco

<title>Resumo</title><p>O texto visa apreender a formação e diversificação da riqueza paulista durante o século XIX. A análise recai sobre os Lacerda Franco, importante família cujos membros principiaram economicamente em atividades de cunho interno (lavoura de mantimentos, criação e comércio de animais, produção de aguardente) nas terras próximas da vila de São Paulo e, posteriormente, migraram para o Oeste Paulista, tornando-se senhores de engenho e cafeicultores. Esse processo de enriquecimento aponta a formação de sociedades agrícolas, casa comissária e exportadora, indústria, banco, diversificando as formas de riqueza dentro do complexo exportador cafeeiro da segunda metade do XIX. O fio condutor do trabalho é a apreensão da dinâmica (movimento) desse processo, materializada, através da documentação da família e de suas empresas – o que diferencia o trabalho das análises correntes apoiadas de forma unívoca em inventários –, de suas estratégias econômicas, nas diferentes atividades que os enriqueceram e nas difusas formas de alocação do capital.</p>

Paradise revealed II: Top science, sunny beach, tropical fruits and caipirinhas….

Some people say that lightning never strikes twice in the same place. Gratefully, sunbeam does! In February 2010, Brazilian scientists organized an outstanding multidisciplinary meeting at a beach resort in Angra dos Reis, Rio de Janeiro, Brazil, that brought together leaders of the cell death, tumor biology and immunology fields. Along with couple of hundred participants, speakers shared their latest work, experience and enthusiasm in an excited atmosphere rocked by the sound of waves.1 Keystone Symposia on Molecular and Cellular Biology and Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP), the Sao Paulo State Research Foundation, decided to surf this idea and worked together to implement the first Keystone meeting in the State of Sao Paulo—the second organized in Brazil. This time the venue was the delightful Enseada beach, in Guaruja, a coastal paradisiacal town located in the south of the State of Sao Paulo. The sophisticated and yet casual hotel, the amazing fine sand beach, the fresh breeze, the tasty fruits and coconut water and, of course, the famous Brazilian caipirinhas provided an incredibly relaxed and friendly atmosphere where top scientists were overwhelmed by the quality and depth of students' interrogations. Organized by Gustavo Amarante-Mendes, Douglas Green and Kim Newton, the event started with a pre-meeting course on Cell Death modalities. The course brought together 60 PhD students or postdocs fully supported by FAPESP, half coming from Brazil and half from abroad, creating a dynamic and highly interactive environment that lasted throughout the meeting. Vishva Dixit (Genentech, Inc., USA) presented the 'Keynote Address' on inflammasome structure and signaling events, describing the activation of non-canonical inflammasome by cytosolic LPS and its role in septic shock. In line with this, Petr Broz (University of Basel, Switzerland) demonstrated that guanylate-binding proteins (GBPs) targeted the bacteria and promoted disruption of bacteria-containing vacuoles, allowing cytosolic sensing of LPS and caspase-11 activation. Guy Salvesen (Sanford-Burnham Medical Research Institute, USA) introduced us to novel specific probes highly specific for each caspase active site, enabling unambiguous discrimination of caspase activation. Mohanish Deshmukh (University of North Carolina at Chapel Hill, USA) demonstrated that cytosolic cytochrome c is not able to engage in the apoptosome formation in neurons because of very low levels of Apaf-1 in these cells, and that free cytosolic cytochrome c is ubiquitinated and degraded by the proteasome. Marion MacFarlane (MRC Toxicologic Unit, UK), demonstrated that caspase-8 and c-FLIP were able to form chains, and that the respective ratio of caspase-8/c-FLIPS/L determines whether the cell would engage the apoptotic pathway or rather continue to live. Necroptotic pathways were extensively discussed by Peter Vandenabeele (VIB, Ghent University, Belgium), Francis Chan (University of Massachussets Medical School, USA) and Kim Newton (Genentech, Inc., USA). Peter Vandenabeele described that RIPK1 protects intestinal epithelial cells (IECs) from apoptosis. RIPK1IEC-KO mice presented increased apoptosis, barrier disruption, bacterial translocation and inflammatory infiltrates, resulting in significant weight loss and lethality. Importantly, antibiotic treatment of RIPK1IEC-KO mice decreased the inflammation and improved survival. Francis Chan revealed that, in dendritic cells, RIPK3 is necessary for TLR4-mediated activation of caspases-8 (requirement for FADD and RIPK1) and -1 (requirement for ROS) and IL-1β processing, and that RIPK3-mediated maturation of IL-1β is critical to injury-induced tissue repair. Kim Newton described that necroptosis-related inflammation is dependent on RIPK1 and RIPK3, but not on MLKL. Douglas Green (St Jude Children's Research Hospital, USA) delivered a captivating lecture in which he approached the question of non-genetic control of cell survival. He presented new results obtained by single-cell mass spectrometry to investigate the cell population that consistently survives TRAIL-induced apoptosis.

111-POS

Methods A total of 24 preeclampsia was enrolled. All pregnant were Caucasian, non-smoker, BMI 30 Kg/m2. At the time of clinic attendance, venous blood samples were collected (EDTA), tubes centrifuged and plasma samples were stored at −70 °C. sFLT-1 plasma levels were measured by ELISA (DVR100B). MiRs were extracted from plasma using the miRNeasy Serum/Plasma Kit. Samples from three preeclampsia presenting the highest level of sFLT-1 and three presenting the lowest levels were choose to performed a screening using the Human Plasma miRNA PCR array (MIHS-106Z) following the manufacturer’s protocol. After screening individual miRNAs were quantified by miScript SYBR Green qRT-PCR assays using specifics primers. Results Among 84 miRNAs evaluated by PCR-array, 4 were differentially expressed between groups considering a fold-change ⩾3.0: miR-195-5p, miR-16-5p and miR-19b-3p were more expressed in high group and miR-375 in low group. The next step was performed real-time qRT-PCR in all samples (n = 24) and verify correlations with sFLT-1. We use two extremes of analysis: 50% and 25% of sFLT-1 levels in the 24 samples (n = 12 in low and n = 12 in high group considering 50% analysis; and n = 6 in low and n = 6 in high group considering 25% analysis). The result is demonstrated in Figure. Conclusions We concluded that miR195-5p is associated with higher levels of sFLT-1 in preeclampsia. Financial Support: Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) and Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq). Disclosures V. Sandrim: None. K. Fernandes: None. R. Cavalli: None.

AFLP markers and composition of alkaloids between populations of Annona crassiflora Mart. of Brazilian savanna

Annona crassiflora Mart. is a native tree from Brazilian savanna, widely spread throughout this biome. Isoquinoline alkaloids are an important characteristic of species of Annonaceae and several biological activities have been reported in the literature concerning these compounds [e.g. 1]. The present work aims to assess the magnitude of genetic diversity among different populations of A. crassiflora using AFLP markers, and verify the existence of any correlation between the AFLP data and the composition of alkaloids [2]. 106 samples of Annona crassiflora from eight populations from Brazilian savanna areas in the states of Sao Paulo, Goias, Minas Gerais and Distrito Federal were analyzed. Regarding the genetic diversity, the percentage of polymorphisms (P) ranged from 23.8% to 62.96%, the average expected heterozygosity (He) ranged from 0.077 to 0.215 and the Shannon's Index ranged from 0.119 to 0.323. These data suggest a low to moderate level of genetic diversity. The molecular analysis of variance (AMOVA) indicates that most of the genetic variation occurs within populations (70%), while interpopulation variation is lower (22%). The FST value was 0.401. The Mantel test (r = 0.107; p = 0.154) showed a weak correlation between geographic distance and genetic distance. No correlation between alkaloid profiles and genetic differentiation was observed (Mantel test, r =-0.084; p = 0.003). Our results may contribute to establishment of conservation strategies for Brazilian savanna, looking forward to avoid genetic losses and ensure the long-term viability of populations of A. crassiflora. Acknowledgements: FAPESP (Fundacao de Amparo a Pesquisa do estado de Sao Paulo) for financial support (2007/0651143 – 0). DYACS is a research fellow of CNPq. Keywords: Annona crassiflora, genetic diversity, AFLP, Isoquinoline alkaloids

Molecular evolution of Zika virus during its emergence in the 20th century

Zika virus (ZIKV) is a mosquito-borne flavivirus first isolated in Uganda in 1947. Although entomological and virologic surveillance have reported ZIKV enzootic activity in diverse countries of Africa and Asia, few human cases were reported until 2007, when a Zika fever epidemic took place in Micronesia. In the context of West Africa, the WHO Collaborating Centre for Arboviruses and Hemorrhagic Fever at Institut Pasteur of Dakar (http://www.pasteur.fr/recherche/banques/ CRORA/) reports the periodic circulation of ZIKV since 1968. Despite several reports on ZIKV, the genetic relationships among viral strains from West Africa remain poorly understood. To evaluate the viral spread and its molecular epidemiology, we investigated 37 ZIKV isolates collected from 1968 to 2002 in six localities in Senegal and Cote d’Ivoire. In addition, we included strains from six other countries. Our results suggested that these two countries in West Africa experienced at least two independent introductions of ZIKV during the 20 century, and that apparently these viral lineages were not restricted by mosquito vector species. Moreover, we present evidence that ZIKV has possibly undergone recombination in nature and that a loss of the N154 glycosylation site in the envelope protein was a possible adaptive response to the Aedes dalzieli vector. Citation: Faye O, Freire CCM, Iamarino A, Faye O, de Oliveira JVC, et al. (2014) Molecular Evolution of Zika Virus during Its Emergence in the 20 Century. PLoS Negl Trop Dis 8(1): e2636. doi:10.1371/journal.pntd.0002636 Editor: Brian Bird, Centers for Disease Control and Prevention, United States of America Received March 4, 2013; Accepted November 27, 2013; Published January 9, 2014 Copyright: 2014 Faye et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This study was made possible by the Institute Pasteur of Dakar in Senegal, FAPESP (Fundacao de Amparo a Pesquisa do Estado de Sao Paulo, Brazil) projects #00/04205-6 (VGDN program), #08/17013-6 and #10/19341-4. CCMF has a CAPES studentship, AI (project #12/04818-5) and JVCdO received FAPESP scholarships and PMAZ holds a CNPq-PQ grant. Funding was also provided by NIH grant R01-AI069145. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * E-mail: asall@pasteur.sn . These authors contributed equally to this work.

Ventilatory muscle strength and quality of life in obese patients undergoing bariatric surgery. Prelimianry results

Introduction Obesity is one of the public health problems more relevant in modern society, leading to a series of changes in mechanical ventilation. Obesity treatment is aimed at improving the health and quality of life. Materials and methods The study included 13 female patients, obese grade III, recruited from two bariatric surgery services and referred to the Sleep Laboratory at the Nove de Julho University. Inclusion criteria included patients who were obese grade III (BMI ⩾ 40 ) or grade II (BMI 35.0–39.9), age between 18 and 65years, accepting voluntarily to participate in the study by reading and signing the informed consent form. Results Mean age was 40.08 ± 9.86, after bariatric surgery the mean body mass index was 36.91 ± 6.67, with p =0.004 and maximum inspiratory pressures were 84.12 ± 9.36 and 82.36 ± 12.21 the maximum expiratory, with a p ?0.001 and p ?0.001 respectively. With the BAROS questionnaire there was an report of good to excellent response to surgery in terms of quality of life in 75% of patients. Conclusion After bariatric surgery an optimization in maximum inspiratory and expiratory pressures was observed. The BAROS questionnaire is standardized and easily applied to evaluate the results after bariatric surgery. Acknowledgements The Sleep Laboratory receives funding from the Universidade Nove de Julho (Brazil) and research projects approved by the Brazilian fostering agencies Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) and Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP). LVFO received a grant from CNPq (Research Productivity modality - PQID, process number 307618/2010–2).

Obstructive sleep apnea and pulmonary function in morbid obesity before and after bariatric surgery: a randomized controlled clinical trial

Introduction The aim of the present study was to assess daytime sleepiness, sleep architecture and pulmonary function in patients with morbid obesity before and after bariatric surgery. Materials and methods Patients were divided into a bariatric surgery group and control group. The clinical evaluation was performed at the Sleep Laboratory of the Universidade Nove de Julho (Sao Paulo, Brazil) and consisted of the collection of clinical data, weight, height, body mass index (BMI), measurements of neck and abdomen circumferences, spirometry, respiratory pressure measurements, full standard polysomnography (PSG) and the administration of the Berlin Questionnaire and Epworth Sleepiness Scale. Results Fifty-two patients participated in the study and underwent PSG, 16 of whom also underwent bariatric surgery. Following surgery, mean BMI decreased from 48.15 ± 8.58 to 36.91 ± 6.67 kg/m 2 . Significant differences were found between the preoperative and postoperative periods regarding neck and waist circumference ( p p p = 0.002 and p = 0.004) and maximum expiratory pressure ( p = 0.001 and p = 0.002) for women and men, respectively, as well as sleep stage N3 ( p 0.001), REM sleep ( p = 0.049) and the apnea–hypopnea index ( p = 0.008) Conclusion Bariatric surgery effectively reduces neck and waist circumference, increases maximum respiratory pressures, enhances sleep architecture and reduces respiratory sleep disorders, specifically obstructive sleep apnea, in patients with morbid obesity. Acknowledgements The Sleep Laboratory receives funding from the Universidade Nove de Julho (Brazil) and research projects approved by the Brazilian fostering agencies Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) and Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP). LVFO received a grant from CNPq (Research Productivity modality - PQID, process number 307618/2010–2).

Correction: Workers’ Compensation Status: Does It Affect Orthopaedic Surgery Outcomes? A Meta-Analysis

The organization listed as providing the grant indicated in the Funding section is incorrect. The correct organization is: FAPESP (Fundacao de Amparo a Pesquisa do Estado de Sao Paulo).

The 1-Year Treatment Outcome of Generalized Chronic Periodontitis May be Enhanced by the Systemic Use of Metronidazole Alone or in Combination With Amoxicillin as Adjuncts to Scaling and Root Planing

Article Title and Bibliographic Information Metronidazole alone or with amoxicillin as adjuncts to non-surgical treatment of chronic periodontitis: a 1-year double-blinded, placebo-controlled, randomized clinical trial. Feres M, Soares GMS, Mendes JAV, Silva MP, Faveri M, Teles R, Socransky SS, Figueiredo LC. J Clin Periodontol 39(12):1149-58. Reviewer Jasim M. Albandar, DDS, DMD, PhD, Diplomate ABP Purpose/Question Is orally administered metronidazole alone or in combination with amoxicillin as adjuncts to scaling and root planing more effective than scaling and root planing alone in the treatment of generalized chronic periodontitis? Source of Funding Foundation: Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) (Foundation for Research Support of the State of Sao Paulo, Brazil) Type of Study/Design Randomized controlled clinical trial Level of Evidence Level 2: Limited-quality, patient-oriented evidence Strength of Recommendation Grade Not applicable

O princípio do acesso livre é parte da essência de nossa profissão

Entrevista a Abel Laerte Packer (Brasil). Coordenador do projeto SciELO (Biblioteca Científica Eletrônica em linha) e assessor da Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP).Magíster em Bibliotecología pela Universidade de Syracuse, Nova York, foi diretor do Centro Latino-Americano e do Caribe de Informação em Ciências da Saúde (BIREME/PAHO/WHO).