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)

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

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

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

Clinical presentation and survival of smear-positive pulmonary tuberculosis patients of a University General Hospital in a developing country

From January 1995 to August 1997 we evaluated prospectively the clinical presentation, laboratory findings and short-term survival of smear-positive pulmonary tuberculosis (TB) patients who sought care at our hospital. After providing informed, written consent, the patients were interviewed and laboratory tests were performed. Information about survivorship and death was collected through September 1998. Eighty-six smear-positive pulmonary TB patients were enrolled; 26.7% were HIV-seropositive. Seventeen HIV-seronegative pulmonary TB patients (19.8%) presented chronic diseases in addition to TB. In the multiple logistic regression analysis a CD4+ cell count or = 50 years were independently associated with decreased survival. Among HIV-seronegative persons, the presence of an additional disease increased the risk of death of almost six-fold. Use of antiretroviral drugs was associated with a lower risk of death among HIV-seropositive smear-positive pulmonary TB patients (RH = 0.32, 95% CI 0.10-0.92). In our study smear-positive pulmonary TB patients had a low short-term survival rate that was strongly associated with HIV infection, age and co-morbidities. Therapy with antiretroviral drugs reduced the short-term risk of death among HIV-seropositive patients after TB diagnosis

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

Natural archives of long-range transported contamination at the remote lake Letšeng-la Letsie, Maloti Mountains, Lesotho

Naturally accumulating archives, such as lake sediments and wetland peats, in remote areas may be used to identify the scale and rates of atmospherically deposited pollutant inputs to natural ecosystems. Co-located lake sediment and wetland cores were collected from Letšeng-la Letsie, a remote lake in the Maloti Mountains of southern Lesotho. The cores were radiometrically dated and analysed for a suite of contaminants including trace metals and metalloids (Hg, Pb, Cu, Ni, Zn, As), fly-ash particles, stable nitrogen isotopes, polycyclic aromatic hydrocarbons (PAHs) and persistent organic pollutants such as polychlorinated biphenyls (PCBs), polybrominated flame retardants (PBDEs) and hexachlorobenzene (HCB). While most trace metals showed no recent enrichment, mercury, fly-ash particles, high molecular weight PAHs and total PCBs showed low but increasing levels of contamination since c.1970, likely the result of long-range transport from coal combustion and other industrial sources in the Highveld region of South Africa. However, back-trajectory analysis revealed that atmospheric transport from this region to southern Lesotho is infrequent and the scale of contamination is low. To our knowledge, these data represent the first palaeolimnological records and the first trace contaminant data for Lesotho, and one of the first multi-pollutant historical records for southern Africa. They therefore provide a baseline for future regional assessments in the context of continued coal combustion in South Africa through to the mid-21st century

Comparison between observed children's tooth brushing habits and those reported by mothers

<p>Abstract</p> <p>Background</p> <p>Information bias can occur in epidemiological studies and compromise scientific outcomes, especially when evaluating information given by a patient regarding their own health. The oral habits of children reported by their mothers are commonly used to evaluate tooth brushing practices and to estimate fluoride intake by children. The aim of the present study was to compare observed tooth-brushing habits of young children using fluoridated toothpaste with those reported by mothers.</p> <p>Methods</p> <p>A sample of 201 mothers and their children (aged 24-48 months) from Montes Claros, Brazil, took part in a cross-sectional study. At day-care centres, the mothers answered a self-administered questionnaire on their child's tooth-brushing habits. The structured questionnaire had six items with two to three possible answers. An appointment was then made with each mother/child pair at day-care centres. The participants were asked to demonstrate the tooth-brushing practice as usually performed at home. A trained examiner observed and documented the procedure. Observed tooth brushing and that reported by mothers were compared for overall agreement using Cohen's Kappa coefficient and the McNemar test.</p> <p>Results</p> <p>Cohen's Kappa values comparing mothers' reports and tooth brushing observed by the examiner ranged from poor-to-good (0.00-0.75). There were statistically significant differences between observed tooth brushing habits and those reported by mothers (p < 0.001). When observed by the examiner, the frequencies of dentifrice dispersed on all bristles (35.9%), children who brushed their teeth alone (33.8%) and those who did not rinse their mouths during brushing (42.0%) were higher than those reported by the mothers (12.1%, 18.9% and 6.5%, respectively; p < 0.001).</p> <p>Conclusions</p> <p>In general, there was low agreement between observed tooth brushing and mothers' reports. Moreover, the different methods of estimation resulted in differences in the frequencies of tooth brushing habits, indicative of reporting bias. Data regarding children's tooth-brushing habits as reported by mothers should be considered with caution in epidemiological surveys on fluoridated dentifrice use and the risk of dental fluorosis.</p