1,410 research outputs found

    The Influence of Orthopedic Surgery on Circulating Metabolite Levels, and their Associations with the Incidence of Postoperative Delirium

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    The mechanisms underlying the occurrence of postoperative delirium development are unclear and measurement of plasma metabolites may improve understanding of its causes. Participants (n = 54) matched for age and gender were sampled from an observational cohort study investigating postoperative delirium. Participants were ≥65 years without a diagnosis of dementia and presented for primary elective hip or knee arthroplasty. Plasma samples collected pre-and postoperatively were grouped as either control (n = 26, aged: 75.8 ± 5.2) or delirium (n = 28, aged: 76.2 ± 5.7). Widespread changes in plasma metabolite levels occurred following surgery. The only metabolites significantly differing between corresponding control and delirium samples were ornithine and spermine. In delirium cases, ornithine was 17.6% higher preoperatively, and spermine was 12.0% higher postoperatively. Changes were not associated with various perioperative factors. In binary logistic regression modeling, these two metabolites did not confer a significantly increased risk of delirium. These findings support the hypothesis that disturbed polyamine metabolism is an underlying factor in delirium that warrants further investigation

    A Self-Reference False Memory Effect in the DRM Paradigm: Evidence from Eastern and Western Samples

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    It is well established that processing information in relation to oneself (i.e., selfreferencing) leads to better memory for that information than processing that same information in relation to others (i.e., other-referencing). However, it is unknown whether self-referencing also leads to more false memories than other-referencing. In the current two experiments with European and East Asian samples, we presented participants the Deese-Roediger/McDermott (DRM) lists together with their own name or other people’s name (i.e., “Trump” in Experiment 1 and “Li Ming” in Experiment 2). We found consistent results across the two experiments; that is, in the self-reference condition, participants had higher true and false memory rates compared to those in the other-reference condition. Moreover, we found that selfreferencing did not exhibit superior mnemonic advantage in terms of net accuracy compared to other-referencing and neutral conditions. These findings are discussed in terms of theoretical frameworks such as spreading activation theories and the fuzzytrace theory. We propose that our results reflect the adaptive nature of memory in the sense that cognitive processes that increase mnemonic efficiency may also increase susceptibility to associative false memories

    A cross-sectional study on attitudes toward gender equality, sexual behavior, positive sexual experiences, and communication about sex among sexually active and non-sexually active adolescents in Bolivia and Ecuador

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    Background: It is widely agreed upon that gender is a key aspect of sexuality however, questions remain on how gender exactly influences adolescents’ sexual health. Objective: The aim of this research was to study correlations between gender equality attitudes and sexual behavior, sexual experiences and communication about sex among sexually active and non-sexually active adolescents in 2 Latin American countries. Design: In 2011, a cross-sectional study was carried out among 5,913 adolescents aged 14–18 in 20 secondary schools in Cochabamba (Bolivia) and 6 secondary schools in Cuenca (Ecuador). Models were built using logistic regressions to assess the predictive value of attitudes toward gender equality on adolescents’ sexual behavior, on experiences and on communication. Results: The analysis shows that sexually active adolescents who consider gender equality as important report higher current use of contraceptives within the couple. They are more likely to describe their last sexual intercourse as a positive experience and consider it easier to talk with their partner about sexuality than sexually experienced adolescents who are less positively inclined toward gender equality. These correlations remained consistent whether the respondent was a boy or a girl. Non-sexually active adolescents, who consider gender equality to be important, are more likely to think that sexual intercourse is a positive experience. They consider it less necessary to have sexual intercourse to maintain a relationship and find it easier to communicate with their girlfriend or boyfriend than sexually non-active adolescents who consider gender equality to be less important. Comparable results were found for boys and girls. Conclusions: Our results suggest that gender equality attitudes have a positive impact on adolescents’ sexual and reproductive health (SRH) and wellbeing. Further research is necessary to better understand the relationship between gender attitudes and specific SRH outcomes such as unwanted teenage pregnancies and sexual pleasure among adolescents worldwide

    In Vivo Carbon-13 Dynamic MRS and MRSI of Normal and Fasted Rat Liver with Hyperpolarized 13C-Pyruvate

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    BACKGROUND: The use of in vivo (13)C nuclear magnetic resonance spectroscopy in probing metabolic pathways to study normal metabolism and characterize disease physiology has been limited by its low sensitivity. However, recent technological advances have enabled greater than 50,000-fold enhancement of liquid-state polarization of metabolically active (13)C substrates, allowing for rapid assessment of (13)C metabolism in vivo. The present study applied hyperpolarized (13)C magnetic resonance spectroscopy to the investigation of liver metabolism, demonstrating for the first time the feasibility of applying this technology to detect differences in liver metabolic states. PROCEDURES: [1-(13)C]pyruvate was hyperpolarized with a dynamic nuclear polarization instrument and injected into normal and fasted rats. The uptake of pyruvate and its conversion to the metabolic products lactate and alanine were observed with slice-localized dynamic magnetic resonance spectroscopy and 3D magnetic resonance spectroscopic imaging (3D-MRSI). RESULTS: Significant differences in lactate to alanine ratio (P < 0.01) between normal and fasted rat liver slice dynamic spectra were observed. 3D-MRSI localized to the fasted livers demonstrated significantly decreased (13)C-alanine levels (P < 0.01) compared to normal. CONCLUSIONS: This study presents the initial demonstration of characterizing metabolic state differences in the liver with hyperpolarized (13)C spectroscopy and shows the ability to detect physiological perturbations in alanine aminotransferase activity, which is an encouraging result for future liver disease investigations with hyperpolarized magnetic resonance technology

    CSF Beta-amyloid 1-42 Concentration Predicts Delirium Following Elective Arthroplasty Surgery in an Observational Cohort Study

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    OBJECTIVE: To test the hypothesis that APOE ε4 status and cerebrospinal fluid (CSF) Aβ42, T-tau and P-tau would independently predict the risk of postoperative delirium. BACKGROUND: Delirium following surgery is common and associated with adverse outcomes. Age and cognitive impairment are consistent risk factors for postoperative delirium. METHODS: This observational cohort study recruited 282 participants aged 65 years or older, without a diagnosis of dementia, admitted for primary elective hip or knee arthroplasty. Cognitive tests were undertaken preoperatively, blood and CSF were sampled at the time of spinal anesthesia, and participants were assessed daily postoperatively for delirium. RESULTS: Increasing age (P = 0.04), preoperative comorbidity (P = 0.03), type of surgery (P = 0.05), intravenous opioid usage (P = 0.04), and low CSF Aβ42 (P < 0.01) were independent predictors of postoperative delirium. CONCLUSIONS: This study is the first to show an independent association between CSF Aβ42 and delirium incidence in an elective surgical population, suggesting that postoperative delirium may indicate incipient Alzheimer disease

    Cetuximab and irinotecan as third-line therapy in advanced colorectal cancer patients: a single centre phase II trial

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    The epidermal growth factor receptor (EGFR), which participates in signalling pathways that are deregulated in cancer cells, is frequently mutated in colorectal-cancer cells. Cetuximab is a monoclonal antibody that specifically blocks the EGFR. We evaluated the efficacy of cetuximab in weekly combination with irinotecan in metastatic colorectal cancer patients refractory to previous treatments based on oxaliplatin or irinotecan. We included 55 heavily pretreated patients (colon/rectum: 34/11, M/F: 16/29, median age 63 years, range: 27–79) whose disease had progressed during or within an oxaliplatin-based first-line chemotherapy and a irinotecan-based second-line regimen. Patients were followed for tumour response and were also evaluated for the time to tumour progression, and safety of treatment. Cetuximab was given at an initial dose of 400 mg m−2, followed by weekly infusions of 250 mg m−2. Irinotecan was administered weekly at the dose of 90 mg m−2. All patients were assessable for treatment efficacy and safety response rate was 25.4% (95% CI: 21.7–39.6%); 38.2% (95 CI: 18.6–39.8%) of patients showed a disease stability as the best response. As a consequence, the overall tumour control rate was 63.6% (95% CI: 46.4–70.6%). The median time to progression was 4.7 months (95% CI: 2.5–7.1 months) and the median survival time was 9.8 months (95% CI: 3.9–10.1 months). The most common G3-4 noncutaneous side toxicities were: diarrhoea (16.4%), fatigue (12.7%) and stomatitis (7.3%). 89.1% of patients developed skin toxicity and 32.6% of cases was of grade 3–4. No allergic reactions were identified at any courses in any patients. Fever was documented in 27.3% of patients and was most commonly recorded after the first administration. Cetuximab has clinically significant activity even in heavily pretreated colorectal cancer patients progressed after both oxaliplatin and irinotecan-based chemotherapy regimens

    MUC4 activates HER2 signalling and enhances the motility of human ovarian cancer cells

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    The mucin MUC4 is a high molecular weight transmembrane glycoprotein. It consists of a mucin-type subunit (MUC4α) and a transmembrane growth factor-like subunit (MUC4β). The mucin MUC4 is overexpressed in many epithelial malignancies including ovarian cancer, suggesting a possible role in the pathogenesis of these cancers. In this study, we investigated the functional role of MUC4 in the human ovarian cancer cell line SKOV3. The mucin MUC4 was ectopically expressed by stable transfection, and its expression was examined by western blot and confocal microscopy analyses. The in vitro studies demonstrated an enhanced motility of MUC4-expressing SKOV3 cells compared with the vector-transfected cells. The mucin MUC4 expression was associated with apparent changes in actin organisation, leading to the formation of microspike, lammelopodia and filopodia-like cellular projections. An enhanced protein expression and activation of HER2, a receptor tyrosine kinase, was also seen, although no significant change was observed in HER-2 transcript levels in the MUC4-transfected SKOV3 cells. Reciprocal co-immunoprecipitation revealed an interaction of MUC4 with HER2. Further, the MUC4-overexpressing SKOV3 cells exhibited an increase in the phosphorylation of focal adhesion kinase (FAK), Akt and ERK, downstream effectors of HER2. Taken together, our findings demonstrate that MUC4 plays a role in ovarian cancer cell motility, in part, by altering actin arrangement and potentiating HER2 downstream signalling in these cells
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