562 research outputs found

    Preoperative Imaging for Perforator Flaps in Reconstructive Surgery

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    Background: Although preoperative imaging of perforator vasculature in planning microvascular reconstruction is commonplace, there has not been any clear demonstration of the evidence for this practice, or data comparing the many available modalities in an evidence-based approach. This article aims to provide an objective, evidence-based review of the literature on this subject.\ud \ud Methods: The evidence supporting the use of various modalities of imaging was investigated by performing focused searches of the PubMed and Medline databases. The articles were ranked according to the criteria set out in March 2009 Oxford Centre for Evidence-Based Medicine definitions. Endpoints comprised objective outcome data supporting the use of imaging, including flap loss, unplanned returns to theater, operative time reduction, and surgeon-reported stress.\ud \ud Results: The objective high level of evidence for any form of preoperative perforator imaging is low with only small number of comparative studies or case series investigating computed tomographic angiography (CTA), magnetic resonance angiography, handheld Doppler, color duplex, and classic angiography. Of all modalities, there is a growing body of level 2b evidence supporting the use of CTA.\ud \ud Conclusion: While further multicenter trials testing hard outcomes are needed to conclusively validate preoperative imaging in reconstructive surgery, sufficient evidence exists to demonstrate that preoperative imaging can statistically improve outcomes, and that CTA is the current gold standard for perforator mapping

    Modular ‘Click-in-Emulsion’ Bone-Targeted Nanogels

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    A new class of nanogel demonstrates modular biodistribution and affinity for bone. Nanogels, ~70 nm in diameter and synthesized via an astoichiometric click-chemistry in-emulsion method, controllably display residual, free clickable functional groups. Functionalization with a bisphosphonate ligand results in significant binding to bone on the inner walls of marrow cavities, liver avoidance, and anti-osteoporotic effects.National Institutes of Health (U.S.) (RO1 DE016516)National Institutes of Health (U.S.) (R01 EB000244)Damon Runyon Cancer Research Foundation (DFS-#2050-10

    Small-diameter TIPS combined with splenic artery embolization in the management of refractory ascites in cirrhotic patients

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    PURPOSEMaximally decreasing portal pressures with transjugular intrahepatic portosystemic shunt (TIPS) is associated with improved ascites control but also increased encephalopathy incidence. Since splenic venous flow contributes to portal hypertension, we assessed if combining small-diameter TIPS with splenic artery embolization could improve ascites while minimizing encephalopathy.METHODSFifty-five patients underwent TIPS creation for refractory ascites. Subjects underwent creation of 8 mm TIPS followed by proximal splenic artery embolization (group A, n=8), or of 8 mm (group B, n=6) or 10 mm TIPS (group C, n=41) without splenic embolization. Data were retrospectively reviewed.RESULTSIn group A, median portosystemic gradient decreased from 19 mmHg to 9 mmHg after TIPS, and 8 mmHg after subsequent splenic artery embolization. In groups B and C, gradient decreased from 15 mmHg to 8 mmHg and 16 mmHg to 6 mmHg. All patients except for one in group A and two in C had greater than 50% reduction in the number of paracenteses in 3 months. Any postprocedural encephalopathy incidence was 62%, 50%, 83% in groups A, B, and C, respectively. Overall, 20% of subjects with 10 mm TIPS required TIPS reduction/closure compared to 7% of subjects with 8 mm TIPS.CONCLUSIONWe found that 8 mm diameter TIPS provided similar ascites control compared to 10 mm TIPS regardless of splenic embolization. While more patients with 10 mm TIPS required reduction/closure for severe encephalopathy, the study was underpowered for definitive assessment. Splenic embolization might have the potential to further decrease portosystemic gradient and ascites as an alternative to dilation of TIPS to 10 mm minimizing the risk of encephalopathy, but larger studies are warranted

    Understanding Urban Demand for Wild Meat in Vietnam: Implications for Conservation Actions

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    Vietnam is a significant consumer of wildlife, particularly wild meat, in urban restaurant settings. To meet this demand, poaching of wildlife is widespread, threatening regional and international biodiversity. Previous interventions to tackle illegal and potentially unsustainable consumption of wild meat in Vietnam have generally focused on limiting supply. While critical, they have been impeded by a lack of resources, the presence of increasingly organised criminal networks and corruption. Attention is, therefore, turning to the consumer, but a paucity of research investigating consumer demand for wild meat will impede the creation of effective consumer-centred interventions. Here we used a mixed-methods research approach comprising a hypothetical choice modelling survey and qualitative interviews to explore the drivers of wild meat consumption and consumer preferences among residents of Ho Chi Minh City, Vietnam. Our findings indicate that demand for wild meat is heterogeneous and highly context specific. Wild-sourced, rare, and expensive wild meat-types are eaten by those situated towards the top of the societal hierarchy to convey wealth and status and are commonly consumed in lucrative business contexts. Cheaper, legal and farmed substitutes for wild-sourced meats are also consumed, but typically in more casual consumption or social drinking settings. We explore the implications of our results for current conservation interventions in Vietnam that attempt to tackle illegal and potentially unsustainable trade in and consumption of wild meat and detail how our research informs future consumer-centric conservation actions

    Cellular and humoral immune responses against the Plasmodium vivax MSP-1(19) malaria vaccine candidate in individuals living in an endemic area in north-eastern Amazon region of Brazil

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    Background: Plasmodium vivax merozoite surface protein-1 (MSP-1) is an antigen considered to be one of the leading malaria vaccine candidates. PvMSP-1 is highly immunogenic and evidences suggest that it is target for protective immunity against asexual blood stages of malaria parasites. Thus, this study aims to evaluate the acquired cellular and antibody immune responses against PvMSP-1 in individuals naturally exposed to malaria infections in a malaria-endemic area in the north-eastern Amazon region of Brazil.Methods: the study was carried out in Paragominas, Para State, in the Brazilian Amazon. Blood samples were collected from 35 individuals with uncomplicated malaria. Peripheral blood mononuclear cells were isolated and the cellular proliferation and activation was analysed in presence of 19 kDa fragment of MSP-1 (PvMSP-1(19)) and Plasmodium falciparum PSS1 crude antigen. Antibodies IgE, IgM, IgG and IgG subclass and the levels of TNF, IFN-gamma and IL-10 were measured by enzyme-linked immunosorbent assay.Results: the prevalence of activated CD4(+) was greater than CD8(+) T cells, in both ex-vivo and in 96 h culture in presence of PvMSP-1(19) and PSS1 antigen. A low proliferative response against PvMSP-1(19) and PSS1 crude antigen after 96 h culture was observed. High plasmatic levels of IFN-gamma and IL-10 as well as lower TNF levels were also detected in malaria patients. However, in the 96 h supernatant culture, the dynamics of cytokine responses differed from those depicted on plasma assays; in presence of PvMSP-1(19) stimulus, higher levels of TNF were noted in supernatant 96 h culture of malaria patient's cells while low levels of IFN-gamma and IL-10 were verified. High frequency of malaria patients presenting antibodies against PvMSP-1(19) was evidenced, regardless class or IgG subclass. PvMSP-1(19)-induced antibodies were predominantly on non-cytophilic subclasses.Conclusions: the results presented here shows that PvMSP-1(19) was able to induce a high cellular activation, leading to production of TNF and emphasizes the high immunogenicity of PvMSP-1(19) in naturally exposed individuals and, therefore, its potential as a malaria vaccine candidate.Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Instituto Oswaldo Cruz (FIOCRUZ, Brazil)Fiocruz MS, Inst Oswaldo Cruz, Lab Pesquisas Malaria, BR-21040900 Rio de Janeiro, RJ, BrazilFiocruz MS, Ctr Pesquisa Diagnost & Treinamento Malaria CPD M, Reference Ctr Malaria Extra Amazonian Reg Secreta, BR-21040900 Rio de Janeiro, RJ, BrazilFiocruz MS, Inst Oswaldo Cruz, Lab Biol Mol & Doencas Endem, BR-21040900 Rio de Janeiro, RJ, BrazilUniv São Paulo, Dept Analises Clin & Toxicol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Microbiol Immunol & Parasitol, São Paulo, BrazilSVS, Inst Evandro Chagas, Programa Ensaios Clin Malaria, Belem, Para, BrazilUniversidade Federal de São Paulo, Dept Microbiol Immunol & Parasitol, São Paulo, BrazilWeb of Scienc

    Factor VIII gene inversions causing severe hemophilia A originate almost exclusively in male germ cells

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    The factor VIII gene, which is defective In hemophilia A, is located in the last megabase of the long arm of the X chromosome. Inversions due to intrachromosomal homologous recombination between mispaired copies of gene A located within intron 22 of the gene and about 500 kb telomeric to it account for nearly half of all cases of severe hemophilia A. We hypothesized that pairing of Xq with its homolog inhibits the Inversion process, and that, therefore, the event originates predominantly in male germ cells. In all 20 informative cases In which the inversion originated in a maternal grandparent, DNA polymorphism analysis determined that it occurred in the male germline. In addition, all but one of 50 mothers of sporadic cases due to an Inversion were carriers. Thus, these data support the hypothesis and Indicate that factor VIII gene inversions leading to severe hemophilia A occur almost exclusively In male germ cell

    Should patients with abnormal liver function tests in primary care be tested for chronic viral hepatitis: cost minimisation analysis based on a comprehensively tested cohort

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    Background Liver function tests (LFTs) are ordered in large numbers in primary care, and the Birmingham and Lambeth Liver Evaluation Testing Strategies (BALLETS) study was set up to assess their usefulness in patients with no pre-existing or self-evident liver disease. All patients were tested for chronic viral hepatitis thereby providing an opportunity to compare various strategies for detection of this serious treatable disease. Methods This study uses data from the BALLETS cohort to compare various testing strategies for viral hepatitis in patients who had received an abnormal LFT result. The aim was to inform a strategy for identification of patients with chronic viral hepatitis. We used a cost-minimisation analysis to define a base case and then calculated the incremental cost per case detected to inform a strategy that could guide testing for chronic viral hepatitis. Results Of the 1,236 study patients with an abnormal LFT, 13 had chronic viral hepatitis (nine hepatitis B and four hepatitis C). The strategy advocated by the current guidelines (repeating the LFT with a view to testing for specific disease if it remained abnormal) was less efficient (more expensive per case detected) than a simple policy of testing all patients for viral hepatitis without repeating LFTs. A more selective strategy of viral testing all patients for viral hepatitis if they were born in countries where viral hepatitis was prevalent provided high efficiency with little loss of sensitivity. A notably high alanine aminotransferase (ALT) level (greater than twice the upper limit of normal) on the initial ALT test had high predictive value, but was insensitive, missing half the cases of viral infection. Conclusions Based on this analysis and on widely accepted clinical principles, a "fast and frugal" heuristic was produced to guide general practitioners with respect to diagnosing cases of viral hepatitis in asymptomatic patients with abnormal LFTs. It recommends testing all patients where a clear clinical indication of infection is present (e.g. evidence of intravenous drug use), followed by testing all patients who originated from countries where viral hepatitis is prevalent, and finally testing those who have a notably raised ALT level (more than twice the upper limit of normal). Patients not picked up by this efficient algorithm had a risk of chronic viral hepatitis that is lower than the general population

    Evaluation of the genetic polymorphism of Plasmodium falciparum P126 protein (SERA or SERP) and its influence on naturally acquired specific antibody responses in malaria-infected individuals living in the Brazilian Amazon

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    <p>Abstract</p> <p>Background</p> <p>The <it>Plasmodium falciparum </it>P126 protein is an asexual blood-stage malaria vaccine candidate antigen. Antibodies against P126 are able to inhibit parasite growth <it>in vitro</it>, and a major parasite-inhibitory epitope has been recently mapped to its 47 kDa N-terminal extremity (octamer repeat domain – OR domain). The OR domain basically consists of six octamer units, but variation in the sequence and number of repeat units may appear in different alleles. The aim of the present study was to investigate the polymorphism of P126 N-terminal region OR domain in <it>P. falciparum </it>isolates from two Brazilian malaria endemic areas and its impact on anti-OR naturally acquired antibodies.</p> <p>Methods</p> <p>The study was carried out in two villages, Candeias do Jamari (Rondonia state) and Peixoto de Azevedo (Mato Grosso state), both located in the south-western part of the Amazon region. The repetitive region of the gene encoding the P126 antigen was PCR amplified and sequenced with the di-deoxy chain termination procedure. The antibody response was evaluated by ELISA with the Nt47 synthetic peptide corresponding to the P126 OR-II domain.</p> <p>Results</p> <p>Only two types of OR fragments were identified in the studied areas, one of 175 bp (OR-I) and other of 199 bp (OR-II). A predominance of the OR-II fragment was observed in Candeias do Jamari whereas in Peixoto de Azevedo both fragments OR-I and OR-II were frequent as well as mixed infection (both fragments simultaneously) reported here for the first time. Comparing the DNA sequencing of OR-I and OR-II fragments, there was a high conservation among predicted amino acid sequences of the P126 N-terminal extremity. Data of immune response demonstrated that the OR domain is highly immunogenic in natural conditions of exposure and that the polymorphism of the OR domain does not apparently influence the specific immune response.</p> <p>Conclusion</p> <p>These findings confirm a limited genetic polymorphism of the P126 OR domain in <it>P. falciparum </it>isolates and that this limited genetic polymorphism does not seem to influence the development of a specific humoral immune response to P126 and its immunogenicity in the studied population.</p
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