Efeitos de Anestésico Local no Tempo Entre Bólus e na Duração do Trabalho de Parto em Patient-Controlled Epidural Analgesia: Estudo Prospectivo de Dois Regimes de Doses Ultra-Baixas com Ropivacaina e Sufentanil

BACKGROUND: Patient-controlled epidural analgesia with low concentrations of anesthetics is effective in reducing labor pain. The aim of this study was to assess and compare two ultra-low dose regimens of ropivacaine and sufentanil (0.1% ropivacaine plus 0.5 μg.ml-1 sufentanil vs. 0.06% ropivacaine plus 0.5 μg.ml-1 sufentanil) on the intervals between boluses and the duration of labor. MATERIAL AND METHODS: In this non-randomized prospective study, conducted between January and July 2010, two groups of parturients received patient-controlled epidural analgesia: Group I (n = 58; 1 mg.ml-1 ropivacaine + 0.5 μg.ml-1 sufentanil) and Group II (n = 57; 0.6 mg.ml-1 ropivacaine + 0.5 μg.ml-1 sufentanil). Rescue doses of ropivacaine at the concentration of the assigned group without sufentanil were administered as necessary. Pain, local anesthetic requirements, neuraxial blockade characteristics, labor and neonatal outcomes, and maternal satisfaction were recorded. RESULTS: The ropivacaine dose was greater in Group I (9.5 [7.7-12.7] mg.h-1 vs. 6.1 [5.1-9.8 mg.h-1], p < 0.001). A time increase between each bolus was observed in Group I (beta = 32.61 min, 95% CI [25.39; 39.82], p < 0.001), whereas a time decrease was observed in Group II (beta = -1.40 min, 95% CI [-2.44; -0.36], p = 0.009). The duration of the second stage of labor in Group I was significantly longer than that in Group II (78 min vs. 65 min, p < 0.001). CONCLUSIONS: Parturients receiving 0.06% ropivacaine exhibited less evidence of cumulative effects and exhibited faster second stage progression than those who received 0.1% ropivacaine

Deciphering the contribution of biofilm to the pathogenesis of peritoneal dialysis infections: characterization and microbial behaviour on dialysis fluids

Infections are major complications in peritoneal dialysis (PD) with a multifactorial etiology that comprises patient, microbial and dialytic factors. This study aimed at investigating the contribution of microbial biofilms on PD catheters to recalcitrant infections and their interplay with PD related-factors. A prospective observational study was performed on 47 patients attending Centro Hospitalar of Porto and Vila Nova de Gaia/Espinho to whom the catheter was removed due to infectious (n = 16) and non-infectious causes (n = 31). Microbial density on the catheter was assessed by culture methods and the isolated microorganisms identified by matrix-assisted laser desorption/ionization time-of-flight intact cell mass spectrometry. The effect of conventional and three biocompatible PD solutions on 16 Coagulase Negative Staphylococci (CNS) and 10 Pseudomonas aeruginosa strains planktonic growth and biofilm formation was evaluated. Cultures were positive in 87.5% of the catheters removed due infectious and 90.3% removed due to non-infectious causes. However, microbial yields were higher on the cuffs of catheters removed due to infection vs. non-infection. Staphylococci (CNS and Staphylococcus aureus) and P. aeruginosa were the predominant species: 32% and 20% in the infection and 43.3% and 22.7% in the non-infection group, respectively. In general, PD solutions had a detrimental effect on planktonic CNS and P. aeruginosa strains growth. All strains formed biofilms in the presence of PD solutions. The solutions had a more detrimental effect on P. aeruginosa than CNS strains. No major differences were observed between conventional and biocompatible solutions, although in icodextrin solution biofilm biomass was lower than in bicarbonate/lactate solution. Overall, we show that microbial biofilm is universal in PD catheters with the subclinical menace of Staphylococci and P. aeruginosa. Cuffs colonization may significantly contribute to infection. PD solutions differentially impact microbial species. This knowledge is important for the development of infection diagnosis, treatment and preventive strategies.This work received support from a Sociedade Portuguesa de Nefrologia (http://www.spnefro.pt) research grant to AR and a Fundação para a Ciência e Tecnologia (http://www.fct.pt) post doc grant (SFRH/BPD/73663/2010) to MM. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Microbiological, histological, immunological, and toxin response to antibiotic treatment in the mouse model of Mycobacterium ulcerans disease.

Mycobacterium ulcerans infection causes a neglected tropical disease known as Buruli ulcer that is now found in poor rural areas of West Africa in numbers that sometimes exceed those reported for another significant mycobacterial disease, leprosy, caused by M. leprae. Unique among mycobacterial diseases, M. ulcerans produces a plasmid-encoded toxin called mycolactone (ML), which is the principal virulence factor and destroys fat cells in subcutaneous tissue. Disease is typically first manifested by the appearance of a nodule that eventually ulcerates and the lesions may continue to spread over limbs or occasionally the trunk. The current standard treatment is 8 weeks of daily rifampin and injections of streptomycin (RS). The treatment kills bacilli and wounds gradually heal. Whether RS treatment actually stops mycolactone production before killing bacilli has been suggested by histopathological analyses of patient lesions. Using a mouse footpad model of M. ulcerans infection where the time of infection and development of lesions can be followed in a controlled manner before and after antibiotic treatment, we have evaluated the progress of infection by assessing bacterial numbers, mycolactone production, the immune response, and lesion histopathology at regular intervals after infection and after antibiotic therapy. We found that RS treatment rapidly reduced gross lesions, bacterial numbers, and ML production as assessed by cytotoxicity assays and mass spectrometric analysis. Histopathological analysis revealed that RS treatment maintained the association of the bacilli with (or within) host cells where they were destroyed whereas lack of treatment resulted in extracellular infection, destruction of host cells, and ultimately lesion ulceration. We propose that RS treatment promotes healing in the host by blocking mycolactone production, which favors the survival of host cells, and by killing M. ulcerans bacilli

Glycosylation of cancer extracellular vesicles: Capture strategies, functional roles and potential clinical applications

Glycans are major constituents of extracellular vesicles (EVs). Alterations in the glycosylation pathway are a common feature of cancer cells, which gives rise to de novo or increased synthesis of particular glycans. Therefore, glycans and glycoproteins have been widely used in the clinic as both stratification and prognosis cancer biomarkers. Interestingly, several of the known tumor-associated glycans have already been identified in cancer EVs, highlighting EV glycosylation as a potential source of circulating cancer biomarkers. These particles are crucial vehicles of cell–cell communication, being able to transfer molecular information and to modulate the recipient cell behavior. The presence of particular glycoconjugates has been described to be important for EV protein sorting, uptake and organ-tropism. Furthermore, specific EV glycans or glycoproteins have been described to be able to distinguish tumor EVs from benign EVs. In this review, the application of EV glycosylation in the development of novel EV detection and capture methodologies is discussed. In addition, we highlight the potential of EV glycosylation in the clinical setting for both cancer biomarker discovery and EV therapeutic delivery strategies.This work was funded by FEDER funds through the Operational Programme for Competitiveness Factors COMPETE 2020 (POCI-01-0145-FEDER-016585; POCI-01-0145-FEDER-007274) and national funds through the Foundation for Science and Technology (FCT), under the projects:PTDC/BBB-EBI/0567/2014 to C.A.R and UID/BIM/04293/2013; and the project NORTE-01-0145-FEDER-000029, supported by Norte Portugal Regional Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF)

Smart biomaterial-based systems for intrinsic stimuli-responsive chronic wound management

Skin chronic wounds are associated with a state of persistent inflammation and often with infection, originating a specific microenvironment characterized by increased temperature, alkaline pH, elevated enzymatic activity, and high levels of reactive oxygen species (ROS). These alterations can be explored as intrinsic triggers in the design of stimuli-responsive biomaterials for the release of bioactive molecules at the wound microenvironment. Stimuli-responsive biomaterials may not only prolong the bioactivity of the therapeutic agents but also synchronize it with the healing stages, tuning the wound treatment. In addition, the high activity of enzymes, such as lysozyme in infected chronic wounds, as well as the shift to a more alkaline pH may be used as biomarkers for early detection of infected and/or non-healing wounds. Overall, although a few shortcomings still need to be addressed before clinical translation, the bioengineered smart formulations highlighted in this review stand out as a new generation of therapies to manage skin chronic wounds.This work was supported by Portuguese funds through FCT-MCTES (Fundação para a Ciência e Tecnologia and Ministério da Ciência, Tecnologia e Ensino Superior) through the project “AntINFECT“ (POCI-01-0145-FEDER-031781, PTDC/NAN-MAT/31781/2017). FCT-MCTES is further acknowledged for funding LAQV-REQUIMTE Research Unit (UIDB/50006/2020). P.A. thanks FCT-MCTES for the doctoral grant SFRH/BD/145471/2019 financially supported by national and European Union funds (ESF – European Social Fund through “Programa Operacional Regional Norte”)

Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal

Lake sediment records of persistent organic pollutants and polycyclic aromatic hydrocarbons in Southern Siberia mirror the changing fortunes of the Russian economy over the past 70 years

Persistent organic pollutants (POPs) and polycyclic aromatic hydrocarbons (PAHs) have previously been detected in the surface sediments, water, and endemic organisms of Lake Baikal, a UNESCO World Heritage Site. The Selenga River is the primary source of freshwater to Lake Baikal, and transports pollutants accumulating in the Selenga River basin to the lake. Sources of POPs and PAHs in the Selenga River basin grew through the 20th century. In the present study, temporal changes in the concentrations of PAHs and POPs were reconstructed from two lakes in the Selenga River basin over the past 150 years using paleolimnological techniques. Increased concentrations in PAHs and PCBs were recorded initially in the 1930s. The 1940s–1980s was the period of greatest exposure to organic contamination, and concentrations of dichlorodiphenyltrichloroethane (DDT), polychlorinated biphenyls (PCBs), hexachlorocyclohexanes (HCHs) and many PAHs peaked between the 1960s and 1980s in the two lakes. Declines in concentrations and fluxes were recorded for most PAHs and POPs in the 1980s and 1990s. Temporal trends in concentrations of total and individual compounds/congeners of PAH, PCBs, and polybrominated diphenyl ethers (PBDEs) indicate the contribution of both local and regional sources of contamination in the 20th and 21st centuries. Temporal variations in contaminants can be linked to economic and industrial growth in the former USSR after World War II and the economic decline of Russia in the late-1980s and early-1990s, as well as global trends in industrialization and development during the mid-20th century

Performance of the CMS Cathode Strip Chambers with Cosmic Rays

The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device in the CMS endcaps. Their performance has been evaluated using data taken during a cosmic ray run in fall 2008. Measured noise levels are low, with the number of noisy channels well below 1%. Coordinate resolution was measured for all types of chambers, and fall in the range 47 microns to 243 microns. The efficiencies for local charged track triggers, for hit and for segments reconstruction were measured, and are above 99%. The timing resolution per layer is approximately 5 ns

Corticosteroid-Induced Immunosuppression ultimately does not compromise the efficacy of antibiotherapy in murine mycobacterium ulcerans Infection

Buruli ulcer (BU) is a necrotizing disease of the skin, subcutaneous tissue and bone caused by Mycobacterium ulcerans. It has been suggested that the immune response developed during the recommended rifampicin/streptomycin (RS) antibiotherapy is protective, contributing to bacterial clearance. On the other hand, paradoxical reactions have been described during or after antibiotherapy, characterized by pathological inflammatory responses. This exacerbated inflammation could be circumvented by immunosuppressive drugs. Therefore, it is important to clarify if the immune system contributes to bacterial clearance during RS antibiotherapy and if immunosuppression hampers the efficacy of the antibiotic regimen. METHODOLOGY/PRINCIPAL FINDINGS: We used the M. ulcerans infection footpad mouse model. Corticosteroid-induced immunosuppression was achieved before experimental infection and maintained during combined RS antibiotherapy by the administration of dexamethasone (DEX). Time-lapsed analyses of macroscopic lesions, bacterial burdens, histology and immunohistochemistry were performed in M. ulcerans-infected footpads. We show here that corticosteroid-immunosuppressed mice are more susceptible to M. ulcerans, with higher bacterial burdens and earlier ulceration. Despite this, macroscopic lesions remised during combined antibiotic/DEX treatment and no viable bacteria were detected in the footpads after RS administration. This was observed despite a delayed kinetics in bacterial clearance, associated with a local reduction of T cell and neutrophil numbers, when compared with immunocompetent RS-treated mice. In addition, no relapse was observed following an additional 3 month period of DEX administration. CONCLUSIONS/SIGNIFICANCE: These findings reveal a major role of the RS bactericidal activity for the resolution of M. ulcerans experimental infections even during immunosuppression, and support clinical investigation on the potential use of corticosteroids or other immunosuppressive/anti-inflammatory drugs for the management of BU patients undergoing paradoxical reactions.This work was supported by a grant from the Health Services of Fundação Calouste Gulbenkian, and the Portuguese Science and Technology Foundation (FCT) fellowships SFRH/BD/41598/2007, SFRH/BPD/64032/2009, SFRH/BPD/68547/2010 and SFRH/BD/33573/2009 to TGM, GT, AGF, and JBG, respectively. MS is a Ciência 2007 fello

Differential expression of genes during mastitis in Holstein-Zebu crossbreed dairy cows

Among the potential public health problems of animal production, infectious-contagious diseases stand out. Mastitis is among the main diseases affecting dairy cattle. One of the most promising options to reduce the problems caused by this disease, besides proper sanitary and management practices, is selective breeding of resistant animals. To shed light on the immune response mechanisms involved in the resistance/susceptibility phenotype to this disease, we quantified the relative expression of the genes IL-2, IL-6, IL-8, IL-12, IFN-γ, TNF-α, TLR-2, SEMA5A, and FEZL in cells of crossbreed dairy cows, divided into two groups, one healthy and the other suffering from clinical mastitis. Total RNA was extracted from the cells in the milk from the animals in each group (with and without clinical mastitis). Gene expression was determined using the real-time PCR method. The levels of gene expression were compared, and the cows with mastitis were found to express 2.5