1,914 research outputs found

    Immobilisation of cell-binding peptides on poly-epsilon-caprolactone (PCL) films: A comparative XPS study of two chemical surface functionalisation methods

    Get PDF
    Successful interaction between cells and biomaterial surfaces is crucial for biomedical devices, and incorporation of peptides such as RGD (Arg-Gly-Asp) at the polymer interface can substantially promote cell adhesion and proliferation. X-ray photoelectron spectroscopy (XPS) has been used to characterise poly-ε-caprolactone (PCL) films modified by aminolysis and the introduction of RGD peptides via carbodiimide (CDI) and thiol-halogen ‘click’ chemistry. The nitrogen signal acts as an elemental indicator for successful attachment, and changes in the chemical environment are reflected in the carbon and oxygen spectra. Chlorine and sulfur provide additional chemical indicators of reaction progress in the thiol method, with the selective nature of the Cl–S reaction reflected in the complete loss of Cl signal and appearance of S, avoiding potential amine-peptide side-reactions. Comparison of the XPS elemental concentrations indicated an estimate of 2–3% peptide functionalisation on the PCL surface for both methods, correlating with the improvement in Schwann cell response observed after peptide immobilisation. The enhanced selectivity of peptide attachment to the polymer surface demonstrated with XPS for the novel method based on thiol chemistry shows its potential for development as a biomimetic scaffold for peripheral nerve injury

    Acute atrial ischemia associates with early but not late new-onset atrial fibrillation in STEMI patients treated with primary PCI: relationship with in-hospital outcomes

    Get PDF
    Abstract Funding Acknowledgements Type of funding sources: None. OnBehalf N/A Background. New-onset atrial fibrillation (NOAF) is known to be a common complication in STEMI patients undergoing primary percutaneous coronary intervention (PCI), which is associated with a negative short- and long-term prognosis. Recently, two distinct phenotypes of NOAF have been described, namely early (EAF) and late NOAF (LAF). However, whether EAF and LAF recognize different pathogenetic mechanisms is unknown. Purpose. To investigate atrial branches occlusion and EAF or LAF onset in STEMI patients undergoing primary PCI. Methods. Retrospective cohort study including 155 STEMI patients. Patients were divided into 3 groups: sinus rhythm (SR), EAF or LAF. Clinical characteristics, angiographic features including occlusion of atrial branches, namely ramus ostia cavae superioris (ROCS), atrio-ventricular node artery (AVNA), right intermediate atrial artery (RIAA) and left intermediate atrial artery (LIAA), were assessed. We also investigated in-hospital complications, death, and a composite of major post-NOAF adverse events (AEs) including cardiogenic shock, acute pulmonary edema, sustained ventricular tachycardia and ventricular fibrillation. Results. Mean age was 63.8 ± 11.9 years; 78.7% of men. NOAF was detected in 22 (14.2%) patients: 10 (6.4%) EAF and 12 LAF (7.7%). Compared to EAF, LAF patients were older (p = 0.013), with higher GRACE risk score (p = 0.014) and Killip class (p = 0.015), depressed ejection fraction (p = 0.007), elevated filling pressures (p = 0.029), higher c-reactive protein (p = 0.014) and more TIMI flow <3 (p = 0.015). As shown in Figure 1, EAF was associated with higher prevalence of occluded ROCS (p = 0.010), AVNA (p = 0.005) and RIAA (p < 0.001), compared to SR. Moreover, EAF patients had more frequently ≥2 diseased atrial branches than SR (19.5%, p < 0.001) and LAF (25%, p < 0.030) patients. In LAF patients, a higher incidence of pre-PCI cardiogenic shock, post-PCI AEs (p = 0.019 vs SR; p = 0.029 vs EAF) and death (p = 0.004 vs SR) was found. Conclusions. The occlusion of atrial branches is associated with early but not late NOAF following STEMI. LAF patients had worse in-hospital AEs and mortality. Abstract Figure

    Optimisation of the RT-PCR detection of immunomagnetically enriched carcinoma cells

    Get PDF
    BACKGROUND: Immunomagnetic enrichment followed by RT-PCR (immunobead RT-PCR) is an efficient methodology to identify disseminated carcinoma cells in the blood and bone marrow. The RT-PCR assays must be both specific for the tumor cells and sufficiently sensitive to enable detection of single tumor cells. We have developed a method to test RT-PCR assays for any cancer. This has been investigated using a panel of RT-PCR markers suitable for the detection of breast cancer cells. METHODS: In the assay, a single cell line-derived tumor cell is added to 100 peripheral blood mononuclear cells (PBMNCs) after which mRNA is isolated and reverse transcribed for RT-PCR analysis. PBMNCs without added tumor cells are used as specificity controls. The previously studied markers epidermal growth factor receptor (EGFR), mammaglobin 1 (MGB1), epithelial cell adhesion molecule (EpCAM/TACSTD1), mucin 1 (MUC1), carcinoembryonic antigen (CEA) were tested. Two new epithelial-specific markers ELF3 and EphB4 were also tested. RESULTS: MUC1 was unsuitable as strong amplification was detected in 100 cell PBMNC controls. Expression of ELF3, EphB4, EpCAM, EGFR, CEA and MGB1 was found to be both specific for the tumor cell, as demonstrated by the absence of a signal in most 100 cell PBMNC controls, and sensitive enough to detect a single tumor cell in 100 PBMNCs using a single round of RT-PCR. CONCLUSIONS: ELF3, EphB4, EpCAM, EGFR, CEA and MGB1 are appropriate RT-PCR markers for use in a marker panel to detect disseminated breast cancer cells after immunomagnetic enrichment

    Modal beam splitter:Determination of the transversal components of an electromagnetic light field

    Get PDF
    The transversal profile of beams can always be defined as a superposition of orthogonal fields, such as optical eigenmodes. Here, we describe a generic method to separate the individual components in a laser beam and map each mode onto its designated detector with low crosstalk. We demonstrate this with the decomposition into Laguerre-Gaussian beams and introduce a distribution over the integer numbers corresponding to the discrete orbital and radial momentum components of the light field. The method is based on determining an eigenmask filter transforming the incident optical eigenmodes to position eigenmodes enabling the detection of the state of the light field using single detectors while minimizing cross talk with respect to the set of filter masks considered.UK Engineering and Physical Sciences Research Council [EP/J01771X/1]This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

    Are mice good models for human neuromuscular disease? Comparing muscle excursions in walking between mice and humans

    Get PDF
    The mouse is one of the most widely used animal models to study neuromuscular diseases and test new therapeutic strategies. However, findings from successful pre-clinical studies using mouse models frequently fail to translate to humans due to various factors. Differences in muscle function between the two species could be crucial but often have been overlooked. The purpose of this study was to evaluate and compare muscle excursions in walking between mice and humans

    Genome-wide study of association and interaction with maternal cytomegalovirus infection suggests new schizophrenia loci.

    Get PDF
    Genetic and environmental components as well as their interaction contribute to the risk of schizophrenia, making it highly relevant to include environmental factors in genetic studies of schizophrenia. This study comprises genome-wide association (GWA) and follow-up analyses of all individuals born in Denmark since 1981 and diagnosed with schizophrenia as well as controls from the same birth cohort. Furthermore, we present the first genome-wide interaction survey of single nucleotide polymorphisms (SNPs) and maternal cytomegalovirus (CMV) infection. The GWA analysis included 888 cases and 882 controls, and the follow-up investigation of the top GWA results was performed in independent Danish (1396 cases and 1803 controls) and German-Dutch (1169 cases, 3714 controls) samples. The SNPs most strongly associated in the single-marker analysis of the combined Danish samples were rs4757144 in ARNTL (P=3.78 × 10(-6)) and rs8057927 in CDH13 (P=1.39 × 10(-5)). Both genes have previously been linked to schizophrenia or other psychiatric disorders. The strongest associated SNP in the combined analysis, including Danish and German-Dutch samples, was rs12922317 in RUNDC2A (P=9.04 × 10(-7)). A region-based analysis summarizing independent signals in segments of 100 kb identified a new region-based genome-wide significant locus overlapping the gene ZEB1 (P=7.0 × 10(-7)). This signal was replicated in the follow-up analysis (P=2.3 × 10(-2)). Significant interaction with maternal CMV infection was found for rs7902091 (P(SNP × CMV)=7.3 × 10(-7)) in CTNNA3, a gene not previously implicated in schizophrenia, stressing the importance of including environmental factors in genetic studies

    Radiolabeled CCK/gastrin peptides for imaging and therapy of CCK2 receptor-expressing tumors

    Get PDF
    Cholecystokinin (CCK) receptors are overexpressed in numerous human cancers, like medullary thyroid carcinomas, small cell lung cancers and stromal ovarian cancers. The specific receptor-binding property of the endogenous ligands for these receptors can be exploited by labeling peptides with a radionuclide and using these as carriers to guide the radioactivity to the tissues that express the receptors. In this way, tumors can be visualized using positron emission tomography and single photon emission computed tomography imaging. A variety of radiolabeled CCK/gastrin-related peptides has been synthesized and characterized for imaging. All peptides have the C-terminal CCK receptor-binding tetrapeptide sequence Trp-Met-Asp-Phe-NH2 in common or derivatives thereof. This review focuses on the development and application of radiolabeled CCK/gastrin peptides for radionuclide imaging and radionuclide therapy of tumors expressing CCK receptors. We discuss both preclinical studies as well as clinical studies with CCK and gastrin peptides

    Clinical implications of gait analysis in the rehabilitation of adult patients with "Prader-Willi" Syndrome: a cross-sectional comparative study ("Prader-Willi" Syndrome vs matched obese patients and healthy subjects)

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>Being severely overweight is a distinctive clinical feature of Prader-Willi Syndrome (PWS). PWS is a complex multisystem disorder, representing the most common form of genetic obesity. The aim of this study was the analysis of the gait pattern of adult subjects with PWS by using three-Dimensional Gait Analysis. The results were compared with those obtained in a group of obese patients and in a group of healthy subjects.</p> <p>Methods</p> <p>Cross-sectional, comparative study: 19 patients with PWS (11 males and 8 females, age: 18–40 years, BMI: 29.3–50.3 kg/m<sup>2</sup>); 14 obese matched patients (5 males and 9 females, age: 18–40 years, BMI: 34.3–45.2 kg/m<sup>2</sup>); 20 healthy subjects (10 males and 10 females, age: 21–41 years, BMI: 19.3–25.4 kg/m<sup>2</sup>). Kinematic and kinetic parameters during walking were assessed by an optoelectronic system and two force platforms.</p> <p>Results</p> <p>PWS adult patients walked slower, had a shorter stride length, a lower cadence and a longer stance phase compared with both matched obese, and healthy subjects. Obese matched patients showed spatio-temporal parameters significantly different from healthy subjects.</p> <p>Furthermore, Range Of Motion (ROM) at knee and ankle, and plantaflexor activity of PWS patients were significantly different between obese and healthy subjects. Obese subjects revealed kinematic and kinetic data similar to healthy subjects.</p> <p>Conclusion</p> <p>PWS subjects had a gait pattern significantly different from obese patients. Despite that, both groups had a similar BMI. We suggest that PWS gait abnormalities may be related to abnormalities in the development of motor skills in childhood, due to precocious obesity. A tailored rehabilitation program in early childhood of PWS patients could prevent gait pattern changes.</p
    corecore