Association of VEGFA-2578 C > A polymorphism with clinicopathological aspects and outcome in follicular lymphoma patients

Univ Estadual Campinas, Fac Med Sci, Campinas, BrazilAC Camargo Canc Ctr, Dept Pathol, Sao Paulo, BrazilUniv Estadual Campinas, Hematol & Hemotherapy Ctr, Campinas, BrazilUniv Fed Sao Paulo, Dept Clin & Expt Oncol, Sao Paulo, BrazilUniv Estadual Campinas, Fac Med Sci, Lab Mol & Investigat Pathol, Campinas, BrazilUniv Fed Sao Paulo, Dept Clin & Expt Oncol, Sao Paulo, BrazilWeb of Scienc

Building The Sugarcane Genome For Biotechnology And Identifying Evolutionary Trends

Background: Sugarcane is the source of sugar in all tropical and subtropical countries and is becoming increasingly important for bio-based fuels. However, its large (10 Gb), polyploid, complex genome has hindered genome based breeding efforts. Here we release the largest and most diverse set of sugarcane genome sequences to date, as part of an on-going initiative to provide a sugarcane genomic information resource, with the ultimate goal of producing a gold standard genome.Results: Three hundred and seventeen chiefly euchromatic BACs were sequenced. A reference set of one thousand four hundred manually-annotated protein-coding genes was generated. A small RNA collection and a RNA-seq library were used to explore expression patterns and the sRNA landscape. In the sucrose and starch metabolism pathway, 16 non-redundant enzyme-encoding genes were identified. One of the sucrose pathway genes, sucrose-6-phosphate phosphohydrolase, is duplicated in sugarcane and sorghum, but not in rice and maize. A diversity analysis of the s6pp duplication region revealed haplotype-structured sequence composition. Examination of hom(e)ologous loci indicate both sequence structural and sRNA landscape variation. A synteny analysis shows that the sugarcane genome has expanded relative to the sorghum genome, largely due to the presence of transposable elements and uncharacterized intergenic and intronic sequences.Conclusion: This release of sugarcane genomic sequences will advance our understanding of sugarcane genetics and contribute to the development of molecular tools for breeding purposes and gene discovery. © 2014 de Setta et al.; licensee BioMed Central Ltd.151European Commission: Agriculture and Rural Development: Sugar http://ec.europa.eu/agriculture/sugar/index_en.htmKellogg, E.A., Evolutionary history of the grasses (2001) Plant Physiol, 125, pp. 1198-1205Grivet, L., Arruda, P., Sugarcane genomics: depicting the complex genome of an important tropical crop (2001) Curr Opin Plant Biol, 5, pp. 122-127Piperidis, G., Piperidis, N., D'Hont, A., Molecular cytogenetic investigation of chromosome composition and transmission in sugarcane (2010) Mol Genet Genomics, 284, pp. 65-73D'Hont, A., Unraveling the genome structure of polyploids using FISH and GISHexamples of sugarcane and banana (2005) Cytogenet Genome Res, 109, pp. 27-33D'Hont, A., Glaszmann, J.C., Sugarcane genome analysis with molecular markers: a first decade of research (2001) Int Soc Sugar Cane Technol Proc XXIV Congr, pp. 556-559Tomkins, J., Yu, Y., Miller-Smith, H., Frisch, D., Woo, S., Wing, R., A bacterial artificial chromosome library for sugarcane (1999) Theor Appl Genet, 99, pp. 419-424Vettore, L., Silva, F.R., Kemper, E.L., Souza, G.M., Silva, A.M., Ferro, M., Henrique-Silva, F., Monteiro-Vitorello, C.B., Analysis and functional annotation of an expressed sequence tag collection for tropical crop sugarcane (2003) Genome Res, 13, pp. 2725-2735Repbase http://www.girinst.org/repbase/Domingues, D.S., Cruz, G.M.Q., Metcalfe, C.J., Nogueira, F.T.S., Vicentini, R., Alves, C.S., Van Sluys, M.-A., Analysis of plant LTR-retrotransposons at the fine-scale family level reveals individual molecular patterns 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Terapêutica de Precisão e suas Perspectivas em um País de Pecuária Heterogênea.

Quando se considera o foco em saúde animal, entende-se terapêutica de precisão como a gestão do conjunto de tecnologias/práticas que podem ser customizadas em função de características individuais para promover ganhos terapêuticos com o uso mínimo e otimizado de medicamentos e produtos biológicos no tratamento e prevenção de enfermidades de animais

Discovery of Markers of Exposure Specific to Bites of Lutzomyia longipalpis, the Vector of Leishmania infantum chagasi in Latin America

Leishmania parasites are transmitted by the bite of an infected vector sand fly that injects salivary molecules into the host skin during feeding. Certain salivary molecules can produce antibodies and can be used as an indicator of exposure to a vector sand fly and potentially the disease it transmits. Here we identified potential markers of specific exposure to the sand fly Lutzomyia longipalpis, the vector of visceral leishmaniasis in Latin America. Initially, we determined which of the salivary proteins produce antibodies in humans, dogs, and foxes from areas endemic for the disease. To identify potential specific markers of vector exposure, we produced nine different recombinant salivary proteins from Lu. longipalpis and tested for their recognition by individuals exposed to another human-biting sand fly, Lu. intermedia, that transmits cutaneous leishmaniasis and commonly occurs in the same endemic areas as Lu. longipalpis. Two of the nine salivary proteins were recognized only by humans exposed to Lu. longipalpis, suggesting they are immunogenic proteins and may be useful in epidemiological studies. The identification of specific salivary proteins as potential markers of exposure to vector sand flies will increase our understanding of vector–human interaction, bring new insights to vector control, and in some instances act as an indicator for risk of acquiring disease

XAF1 as a modifier of p53 function and cancer susceptibility

Cancer risk is highly variable in carriers of the common TP53-R337H founder allele, possibly due to the influence of modifier genes. Whole-genome sequencing identified a variant in the tumor suppressor XAF1 (E134*/Glu134Ter/rs146752602) in a subset of R337H carriers. Haplotype-defining variants were verified in 203 patients with cancer, 582 relatives, and 42,438 newborns. The compound mutant haplotype was enriched in patients with cancer, conferring risk for sarcoma (P = 0.003) and subsequent malignancies (P = 0.006). Functional analyses demonstrated that wild-type XAF1 enhances transactivation of wild-type and hypomorphic TP53 variants, whereas XAF1-E134* is markedly attenuated in this activity. We propose that cosegregation of XAF1-E134* and TP53-R337H mutations leads to a more aggressive cancer phenotype than TP53-R337H alone, with implications for genetic counseling and clinical management of hypomorphic TP53 mutant carriers.Fil: Pinto, Emilia M.. St. Jude Children's Research Hospital; Estados UnidosFil: Figueiredo, Bonald C.. Instituto de Pesquisa Pelé Pequeno Principe; BrasilFil: Chen, Wenan. St. Jude Children's Research Hospital; Estados UnidosFil: Galvao, Henrique C.R.. Hospital de Câncer de Barretos; BrasilFil: Formiga, Maria Nirvana. A.c.camargo Cancer Center; BrasilFil: Fragoso, Maria Candida B.V.. Universidade de Sao Paulo; BrasilFil: Ashton Prolla, Patricia. Universidade Federal do Rio Grande do Sul; BrasilFil: Ribeiro, Enilze M.S.F.. Universidade Federal do Paraná; BrasilFil: Felix, Gabriela. Universidade Federal da Bahia; BrasilFil: Costa, Tatiana E.B.. Hospital Infantil Joana de Gusmao; BrasilFil: Savage, Sharon A.. National Cancer Institute; Estados UnidosFil: Yeager, Meredith. National Cancer Institute; Estados UnidosFil: Palmero, Edenir I.. Hospital de Câncer de Barretos; BrasilFil: Volc, Sahlua. Hospital de Câncer de Barretos; BrasilFil: Salvador, Hector. Hospital Sant Joan de Deu Barcelona; EspañaFil: Fuster Soler, Jose Luis. Hospital Clínico Universitario Virgen de la Arrixaca; EspañaFil: Lavarino, Cinzia. Hospital Sant Joan de Deu Barcelona; EspañaFil: Chantada, Guillermo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. St. Jude Children's Research Hospital; Estados UnidosFil: Vaur, Dominique. Comprehensive Cancer Center François Baclesse; FranciaFil: Odone Filho, Vicente. Universidade de Sao Paulo; BrasilFil: Brugières, Laurence. Institut de Cancerologie Gustave Roussy; FranciaFil: Else, Tobias. University of Michigan; Estados UnidosFil: Stoffel, Elena M.. University of Michigan; Estados UnidosFil: Maxwell, Kara N.. University of Pennsylvania; Estados UnidosFil: Achatz, Maria Isabel. Hospital Sirio-libanês; BrasilFil: Kowalski, Luis. A.c.camargo Cancer Center; BrasilFil: De Andrade, Kelvin C.. National Cancer Institute; Estados UnidosFil: Pappo, Alberto. St. Jude Children's Research Hospital; Estados UnidosFil: Letouze, Eric. Centre de Recherche Des Cordeliers; FranciaFil: Latronico, Ana Claudia. Universidade de Sao Paulo; BrasilFil: Mendonca, Berenice B.. Universidade de Sao Paulo; BrasilFil: Almeida, Madson Q.. Universidade de Sao Paulo; BrasilFil: Brondani, Vania B.. Universidade de Sao Paulo; BrasilFil: Bittar, Camila M.. Universidade Federal do Rio Grande do Sul; BrasilFil: Soares, Emerson W.S.. Hospital Do Câncer de Cascavel; BrasilFil: Mathias, Carolina. Universidade Federal do Paraná; BrasilFil: Ramos, Cintia R.N.. Hospital de Câncer de Barretos; BrasilFil: Machado, Moara. National Cancer Institute; Estados UnidosFil: Zhou, Weiyin. National Cancer Institute; Estados UnidosFil: Jones, Kristine. National Cancer Institute; Estados UnidosFil: Vogt, Aurelie. National Cancer Institute; Estados UnidosFil: Klincha, Payal P.. National Cancer Institute; Estados UnidosFil: Santiago, Karina M.. A.c.camargo Cancer Center; BrasilFil: Komechen, Heloisa. Instituto de Pesquisa Pelé Pequeno Principe; BrasilFil: Paraizo, Mariana M.. Instituto de Pesquisa Pelé Pequeno Principe; BrasilFil: Parise, Ivy Z.S.. Instituto de Pesquisa Pelé Pequeno Principe; BrasilFil: Hamilton, Kayla V.. St. Jude Children's Research Hospital; Estados UnidosFil: Wang, Jinling. St. Jude Children's Research Hospital; Estados UnidosFil: Rampersaud, Evadnie. St. Jude Children's Research Hospital; Estados UnidosFil: Clay, Michael R.. St. Jude Children's Research Hospital; Estados UnidosFil: Murphy, Andrew J.. St. Jude Children's Research Hospital; Estados UnidosFil: Lalli, Enzo. Institut de Pharmacologie Moléculaire et Cellulaire; FranciaFil: Nichols, Kim E.. St. Jude Children's Research Hospital; Estados UnidosFil: Ribeiro, Raul C.. St. Jude Children's Research Hospital; Estados UnidosFil: Rodriguez-Galindo, Carlos. St. Jude Children's Research Hospital; Estados UnidosFil: Korbonits, Marta. Queen Mary University of London; Reino UnidoFil: Zhang, Jinghui. St. Jude Children's Research Hospital; Estados UnidosFil: Thomas, Mark G.. Colegio Universitario de Londres; Reino UnidoFil: Connelly, Jon P.. St. Jude Children's Research Hospital; Estados UnidosFil: Pruett-Miller, Shondra. St. Jude Children's Research Hospital; Estados UnidosFil: Diekmann, Yoan. Colegio Universitario de Londres; Reino UnidoFil: Neale, Geoffrey. St. Jude Children's Research Hospital; Estados UnidosFil: Wu, Gang. St. Jude Children's Research Hospital; Estados UnidosFil: Zambetti, Gerard P.. St. Jude Children's Research Hospital; Estados Unido

American palm ethnomedicine: A meta-analysis

<p>Abstract</p> <p>Background</p> <p>Many recent papers have documented the phytochemical and pharmacological bases for the use of palms (<it>Arecaceae</it>) in ethnomedicine. Early publications were based almost entirely on interviews that solicited local knowledge. More recently, ethnobotanically guided searches for new medicinal plants have proven more successful than random sampling for identifying plants that contain biodynamic ingredients. However, limited laboratory time and the high cost of clinical trials make it difficult to test all potential medicinal plants in the search for new drug candidates. The purpose of this study was to summarize and analyze previous studies on the medicinal uses of American palms in order to narrow down the search for new palm-derived medicines.</p> <p>Methods</p> <p>Relevant literature was surveyed and data was extracted and organized into medicinal use categories. We focused on more recent literature than that considered in a review published 25 years ago. We included phytochemical and pharmacological research that explored the importance of American palms in ethnomedicine.</p> <p>Results</p> <p>Of 730 species of American palms, we found evidence that 106 species had known medicinal uses, ranging from treatments for diabetes and leishmaniasis to prostatic hyperplasia. Thus, the number of American palm species with known uses had increased from 48 to 106 over the last quarter of a century. Furthermore, the pharmacological bases for many of the effects are now understood.</p> <p>Conclusions</p> <p>Palms are important in American ethnomedicine. Some, like <it>Serenoa repens </it>and <it>Roystonea regia</it>, are the sources of drugs that have been approved for medicinal uses. In contrast, recent ethnopharmacological studies suggested that many of the reported uses of several other palms do not appear to have a strong physiological basis. This study has provided a useful assessment of the ethnobotanical and pharmacological data available on palms.</p

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

AIM: The SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery. METHODS: This was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin. RESULTS: Overall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P < 0.001). After adjustment, delay was not associated with a lower rate of complete resection (OR 1.18, 95% CI 0.90-1.55, P = 0.224), which was consistent in elective patients only (OR 0.94, 95% CI 0.69-1.27, P = 0.672). Longer delays were not associated with poorer outcomes. CONCLUSION: One in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease

XAF1 as a modifier of p53 function and cancer susceptibility

Cancer risk is highly variable in carriers of the common TP53-R337H founder allele, possibly due to the influence of modifier genes. Whole-genome sequencing identified a variant in the tumor suppressor XAF1 (E134*/Glu134Ter/rs146752602) in a subset of R337H carriers. Haplotype-defining variants were verified in 203 patients with cancer, 582 relatives, and 42,438 newborns. The compound mutant haplotype was enriched in patients with cancer, conferring risk for sarcoma (P = 0.003) and subsequent malignancies (P = 0.006). Functional analyses demonstrated that wild-type XAF1 enhances transactivation of wild-type and hypomorphic TP53 variants, whereas XAF1-E134* is markedly attenuated in this activity. We propose that cosegregation of XAF1-E134* and TP53-R337H mutations leads to a more aggressive cancer phenotype than TP53-R337H alone, with implications for genetic counseling and clinical management of hypomorphic TP53 mutant carriers

Rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART): Study protocol for a randomized controlled trial

Background: Acute respiratory distress syndrome (ARDS) is associated with high in-hospital mortality. Alveolar recruitment followed by ventilation at optimal titrated PEEP may reduce ventilator-induced lung injury and improve oxygenation in patients with ARDS, but the effects on mortality and other clinical outcomes remain unknown. This article reports the rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART). Methods/Design: ART is a pragmatic, multicenter, randomized (concealed), controlled trial, which aims to determine if maximum stepwise alveolar recruitment associated with PEEP titration is able to increase 28-day survival in patients with ARDS compared to conventional treatment (ARDSNet strategy). We will enroll adult patients with ARDS of less than 72 h duration. The intervention group will receive an alveolar recruitment maneuver, with stepwise increases of PEEP achieving 45 cmH(2)O and peak pressure of 60 cmH2O, followed by ventilation with optimal PEEP titrated according to the static compliance of the respiratory system. In the control group, mechanical ventilation will follow a conventional protocol (ARDSNet). In both groups, we will use controlled volume mode with low tidal volumes (4 to 6 mL/kg of predicted body weight) and targeting plateau pressure &lt;= 30 cmH2O. The primary outcome is 28-day survival, and the secondary outcomes are: length of ICU stay; length of hospital stay; pneumothorax requiring chest tube during first 7 days; barotrauma during first 7 days; mechanical ventilation-free days from days 1 to 28; ICU, in-hospital, and 6-month survival. ART is an event-guided trial planned to last until 520 events (deaths within 28 days) are observed. These events allow detection of a hazard ratio of 0.75, with 90% power and two-tailed type I error of 5%. All analysis will follow the intention-to-treat principle. Discussion: If the ART strategy with maximum recruitment and PEEP titration improves 28-day survival, this will represent a notable advance to the care of ARDS patients. Conversely, if the ART strategy is similar or inferior to the current evidence-based strategy (ARDSNet), this should also change current practice as many institutions routinely employ recruitment maneuvers and set PEEP levels according to some titration method.Hospital do Coracao (HCor) as part of the Program 'Hospitais de Excelencia a Servico do SUS (PROADI-SUS)'Brazilian Ministry of Healt