Autologous microsurgical breast reconstruction and coronary artery bypass grafting: an anatomical study and clinical implications

OBJECTIVE: To identify possible avenues of sparing the internal mammary artery (IMA) for coronary artery bypass grafting (CABG) in women undergoing autologous breast reconstruction with deep inferior epigastric artery perforator (DIEP) flaps. BACKGROUND: Optimal autologous reconstruction of the breast and coronary artery bypass grafting (CABG) are often mutually exclusive as they both require utilisation of the IMA as the preferred arterial conduit. Given the prevalence of both breast cancer and coronary artery disease, this is an important issue for women's health as women with DIEP flap reconstructions and women at increased risk of developing coronary artery disease are potentially restricted from receiving this reconstructive option should the other condition arise. METHODS: The largest clinical and cadaveric anatomical study (n=315) to date was performed, investigating four solutions to this predicament by correlating the precise requirements of breast reconstruction and CABG against the anatomical features of the in situ IMAs. This information was supplemented by a thorough literature review. RESULTS: Minimum lengths of the left and right IMA needed for grafting to the left-anterior descending artery are 160.08 and 177.80 mm, respectively. Based on anatomical findings, the suitable options for anastomosis to each intercostals space are offered. In addition, 87-91% of patients have IMA perforator vessels to which DIEP flaps can be anastomosed in the first- and second-intercostal spaces. CONCLUSION: We outline five methods of preserving the IMA for future CABG: (1) lowering the level of DIEP flaps to the fourth- and fifth-intercostals spaces, (2) using the DIEP pedicle as an intermediary for CABG, (3) using IMA perforators to spare the IMA proper, (4) using and end-to-side anastomosis between the DIEP pedicle and IMA and (5) anastomosis of DIEP flaps using retrograde flow from the distal IMA. With careful patient selection, we hypothesize using the IMA for autologous breast reconstruction need not be an absolute contraindication for future CABG

Regulation of immunity during visceral Leishmania infection

Unicellular eukaryotes of the genus Leishmania are collectively responsible for a heterogeneous group of diseases known as leishmaniasis. The visceral form of leishmaniasis, caused by L. donovani or L. infantum, is a devastating condition, claiming 20,000 to 40,000 lives annually, with particular incidence in some of the poorest regions of the world. Immunity to Leishmania depends on the development of protective type I immune responses capable of activating infected phagocytes to kill intracellular amastigotes. However, despite the induction of protective responses, disease progresses due to a multitude of factors that impede an optimal response. These include the action of suppressive cytokines, exhaustion of specific T cells, loss of lymphoid tissue architecture and a defective humoral response. We will review how these responses are orchestrated during the course of infection, including both early and chronic stages, focusing on the spleen and the liver, which are the main target organs of visceral Leishmania in the host. A comprehensive understanding of the immune events that occur during visceral Leishmania infection is crucial for the implementation of immunotherapeutic approaches that complement the current anti-Leishmania chemotherapy and the development of effective vaccines to prevent disease.The research leading to these results has received funding from the European Community’s Seventh Framework Programme under grant agreement No.602773 (Project KINDRED). VR is supported by a post-doctoral fellowship granted by the KINDReD consortium. RS thanks the Foundation for Science and Technology (FCT) for an Investigator Grant (IF/00021/2014). This work was supported by grants to JE from ANR (LEISH-APO, France), Partenariat Hubert Curien (PHC) (program Volubilis, MA/11/262). JE acknowledges the support of the Canada Research Chair Program

Receptor-targeted liposome-peptide-siRNA nanoparticles represent a novel and efficient therapeutic approach to prevent conjunctival fibrosis.

There is increasing evidence that the Myocardin-related transcription factor/Serum response factor (MRTF/SRF) pathway plays a key role in fibroblast activation and that knocking down MRTF can lead to reduced scarring and fibrosis. Here, we have developed a receptor-targeted liposome-peptide-siRNA nanoparticle as a non-viral delivery system for MRTF-B siRNA in conjunctival fibrosis. Using 50 nM siRNA, the MRTF-B gene was efficiently silenced by 76% and 72% with LYR and LER nanoparticles, respectively. The silencing efficiency was low when non-targeting peptides or siRNA alone or liposome-siRNA alone were used. LYR and LER nanoparticles also showed higher silencing efficiency than PEGylated LYR-P and LER-P nanoparticles. The nanoparticles were not cytotoxic using different liposomes, targeting peptides, and 50 nM siRNA. Three-dimensional fibroblast-populated collagen matrices were also used as a functional assay to measure contraction in vitro, and showed that MRTF-B LYR nanoparticles completely blocked matrix contraction after a single transfection treatment. In conclusion, this is the first study to develop and show that receptor-targeted liposome-peptide-siRNA nanoparticles represent an efficient and safe non-viral siRNA delivery system that could be used to prevent fibrosis after glaucoma filtration surgery and other contractile scarring conditions in the eye

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

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Development of microsatellite markers for identifying Brazilian Coffea arabica varieties

Microsatellite markers, also known as SSRs (Simple Sequence Repeats), have proved to be excellent tools for identifying variety and determining genetic relationships. A set of 127 SSR markers was used to analyze genetic similarity in twenty five Coffea arabica varieties. These were composed of nineteen commercially important Brazilians and six interspecific hybrids of Coffea arabica, Coffea canephora and Coffealiberica. The set used comprised 52 newly developed SSR markers derived from microsatellite enriched libraries, 56 designed on the basis of coffee SSR sequences available from public databases, 6 already published, and 13 universal chloroplast microsatellite markers. Only 22 were polymorphic, these detecting 2-7 alleles per marker, an average of 2.5. Based on the banding patterns generated by polymorphic SSR loci, the set of twenty-five coffee varieties were clustered into two main groups, one composed of only Brazilian varieties, and the other of interspecific hybrids, with a few Brazilians. Color mutants could not be separated. Clustering was in accordance with material genealogy thereby revealing high similarity

Sugarcane (Saccharum X officinarum): A Reference Study for the Regulation of Genetically Modified Cultivars in Brazil

Global interest in sugarcane has increased significantly in recent years due to its economic impact on sustainable energy production. Sugarcane breeding and better agronomic practices have contributed to a huge increase in sugarcane yield in the last 30 years. Additional increases in sugarcane yield are expected to result from the use of biotechnology tools in the near future. Genetically modified (GM) sugarcane that incorporates genes to increase resistance to biotic and abiotic stresses could play a major role in achieving this goal. However, to bring GM sugarcane to the market, it is necessary to follow a regulatory process that will evaluate the environmental and health impacts of this crop. The regulatory review process is usually accomplished through a comparison of the biology and composition of the GM cultivar and a non-GM counterpart. This review intends to provide information on non-GM sugarcane biology, genetics, breeding, agronomic management, processing, products and byproducts, as well as the current technologies used to develop GM sugarcane, with the aim of assisting regulators in the decision-making process regarding the commercial release of GM sugarcane cultivars

Dental pulp tissue engineering

Dental pulp is a highly specialized mesenchymal tissue, which have a restrict regeneration capacity due to anatomical arrangement and post-mitotic nature of odontoblastic cells. Entire pulp amputation followed by pulp-space disinfection and filling with an artificial material cause loss of a significant amount of dentin leaving as life-lasting sequelae a non-vital and weakened tooth. However, regenerative endodontics is an emerging field of modern tissue engineering that demonstrated promising results using stem cells associated with scaffolds and responsive molecules. Thereby, this article will review the most recent endeavors to regenerate pulp tissue based on tissue engineering principles and providing insightful information to readers about the different aspects enrolled in tissue engineering. Here, we speculate that the search for the ideal combination of cells, scaffolds, and morphogenic factors for dental pulp tissue engineering may be extended over future years and result in significant advances in other areas of dental and craniofacial research. The finds collected in our review showed that we are now at a stage in which engineering a complex tissue, such as the dental pulp, is no longer an unachievable and the next decade will certainly be an exciting time for dental and craniofacial research

Contribuição da biópsia pulmonar a céu aberto na avaliação de pneumopatias difusas e agudas em unidade de terapia intensiva pediátrica

Introdução: Os dados clínico-laboratoriais convencionais raramente fornecem o diagnóstico em pneumopatias difusas. O objetivo deste estudo foi avaliar o papel da biópsia pulmonar a céu aberto no que se refere ao seu potencial diagnóstico, ao impacto dos resultados sobre a conduta clínica e à incidência de complicações do procedimento. Material e métodos: No período de janeiro/1987 a janeiro/1997, 29 biópsias pulmonares foram realizadas em crianças com pneumopatias difusas, em insuficiência respiratória aguda, sem etiologia e sem resposta à terapêutica empírica prévia. Foram excluídos os recém-nascidos, crianças com pneumopatias crônicas prévias e crianças com coagulopatia ou choque intratáveis. Todas as biópsias foram realizadas através de microtoracotomia no pulmão mais acometido ao exame radiológico. O fragmento de tecido pulmonar foi analisado por meio de culturas e de exames de microscopia ótica, eletrônica e imunofluorescência. Resultados: O processamento do material da biópsia forneceu pelo menos um diagnóstico histopatológico em todas as crianças estudadas (100%) e em 20 (68,9%) obteve-se um diagnóstico etiológico. Os principais diagnósticos histopatológicos foram: pneumonite intersticial não específica com fibrose variável em 18 casos; bronquiolite em oito casos e hipertensão pulmonar em três casos. Nos diagnósticos etiológicos, os principais agentes foram: citomegalovírus em seis crianças; Pneumocystis carinii em três; adenovírus em três e infecção pelo vírus respiratório sincicial em três casos. Os resultados geraram mudanças no tratamento em 20 casos (68,9%). As principais alterações de conduta foram a introdução de corticoterapia em 14 pacientes e a revisão da antibioticoterapia em seis. Sete casos (24,1%) apresentaram complicações, que foram resolvidas, e nenhum óbito foi relacionado ao procedimento. Conclusão: Conclui-se que a biópsia pulmonar a céu aberto é um procedimento que, mesmo invasivo, deve ser considerado na avaliação de crianças com pneumopatias difusas graves, sem etiologia definida, sem resposta à terapêutica previamente instituída e em insuficiência respiratória.<br>Introduction: The diagnosis of diffuse lung disease is still a challenge for the pediatric intensive care physician. Routine clinical examinations and laboratory tests are frequently negative. The objective of this study was to evaluate the diagnostic potential, the impact on therapy and the rate of complications of open lung biopsy in children with undiagnosed diffuse lung disease, respiratory failure and inappropriate response to initial therapy. Methods: From January 1987 to January 1997, 29 children with diffuse pulmonary disease of unknown etiology, respiratory failure (PaO2/FiO2 < 300) and no response to previous treatments were considered for open lung biopsy. Newborns, children with known chronic pulmonary disease and children with untreatable shock or coagulopathy were excluded. All biopsies were performed by a thoracic surgeon by a microthoracotomy in the lung shown to be the most affected by X-ray examination. Tissue samples were analyzed in terms of cultures, light microscopy, electron microscopy and immunofluorescence microscopy, according to the pathologist's decision. Results: All biopsies (100%) resulted in at least one histological diagnosis and in 20 patients (68.9%) it was obtained a specific diagnosis. The most frequent histological patterns found were: non-specific interstitial pneumonitis with variable degrees of fibrosis in 18 cases; bronchiolitis in eight cases and pulmonary hypertension in three cases. Regarding the most frequent specific diagnosis, six children were found with cytomegalovirus infection, three with Pneumocystis carinii, three with adenovirus and three with respiratory syncytial virus infection. These data induced a change in therapy in 20 children (68.9%). The most frequent changes in therapy were the use of corticosteroids in 14 children and a review of the antibiotic regimen in six patients. Seven patients (24.1%) presented with complications that were easily resolved. There were 13 deaths, probably due to the critical conditions of these patients, all unrelated to the procedure. Conclusions: Open lung biopsy, though an invasive procedure, should be considered in the evaluation of selected children with undiagnosed diffuse lung disease, respiratory failure and with no satisfactory response to previous therapies