Alien Registration- Contois, Henri J. (Sanford, York County)

https://digitalmaine.com/alien_docs/3121/thumbnail.jp

Alien Registration- Contois, Wilfrid J. (Sanford, York County)

https://digitalmaine.com/alien_docs/3124/thumbnail.jp

Alien Registration- Contois, Roland J. (Sanford, York County)

https://digitalmaine.com/alien_docs/3123/thumbnail.jp

Public Awareness of Medical Imaging as a Source of Ionizing Radiation Exposure

Background. Biological effects of exposure to ionizing radiation (IR) are well known. Literature suggests most patients and physicians lack proficient understanding of risks associated with ionizing radiation. Our study goals were to: assess the extent to which productive, informed conversations regarding ionizing radiation are occurring between patients and providers; characterize public awareness of medical imaging procedures as sources of IR exposure; and investigate best practices in patientprovider communications. Methods. We developed and administered a 17-question survey to 303 adults at five locations across Chittenden County, Vermont, over a 6-week period in fall 2016. Descriptive and statistical analyses were conducted using SPSS. Results. The three age groups of respondents had different knowledge levels about ionizing radiation (p Conclusions/Recommendations. 1. A standard oral presentation for pre-imaging patient-provider communication, along with a written handout, be developed; 2. A section of the electronic medical record (also accessible through the patient portal) containing IR exposure be created for patients and physicians to track individuals\u27 information.https://scholarworks.uvm.edu/comphp_gallery/1249/thumbnail.jp

A blood-based diagnostic test incorporating plasma Aβ42/40 ratio, ApoE proteotype, and age accurately identifies brain amyloid status: Findings from a multi cohort validity analysis

BACKGROUND: The development of blood-based biomarker tests that are accurate and robust for Alzheimer\u27s disease (AD) pathology have the potential to aid clinical diagnosis and facilitate enrollment in AD drug trials. We developed a high-resolution mass spectrometry (MS)-based test that quantifies plasma Aβ42 and Aβ40 concentrations and identifies the ApoE proteotype. We evaluated robustness, clinical performance, and commercial viability of this MS biomarker assay for distinguishing brain amyloid status. METHODS: We used the novel MS assay to analyze 414 plasma samples that were collected, processed, and stored using site-specific protocols, from six independent US cohorts. We used receiver operating characteristic curve (ROC) analyses to assess assay performance and accuracy for predicting amyloid status (positive, negative, and standard uptake value ratio; SUVR). After plasma analysis, sites shared brain amyloid status, defined using diverse, site-specific methods and cutoff values; amyloid PET imaging using various tracers or CSF Aβ42/40 ratio. RESULTS: Plasma Aβ42/40 ratio was significantly (p \u3c 0.001) lower in the amyloid positive vs. negative participants in each cohort. The area under the ROC curve (AUC-ROC) was 0.81 (95% CI = 0.77-0.85) and the percent agreement between plasma Aβ42/40 and amyloid positivity was 75% at the optimal (Youden index) cutoff value. The AUC-ROC (0.86; 95% CI = 0.82-0.90) and accuracy (81%) for the plasma Aβ42/40 ratio improved after controlling for cohort heterogeneity. The AUC-ROC (0.90; 95% CI = 0.87-0.93) and accuracy (86%) improved further when Aβ42/40, ApoE4 copy number and participant age were included in the model. CONCLUSIONS: This mass spectrometry-based plasma biomarker test: has strong diagnostic performance; can accurately distinguish brain amyloid positive from amyloid negative individuals; may aid in the diagnostic evaluation process for Alzheimer\u27s disease; and may enhance the efficiency of enrolling participants into Alzheimer\u27s disease drug trials

The evolution of selective analyses of HDL and LDL cholesterol in clinical and point of care testing

Cardiovascular disease is a leading cause of death worldwide and is caused by the build up of atherosclerotic plaques in the vasculature. It is now well established that the formation of these plaques is closely related to levels of both high density lipoprotein (HDL) and low density lipoprotein (LDL) cholesterol. Thus, the importance of the effective measurement of these is critical for the improved diagnosis and management of atherosclerosis. This review discusses the emergence of methodologies for the selective determination of both LDL and HDL cholesterol. It begins with an explanation of the first methodologies based on ultracentrifugation and precipitation techniques, the development of reference methods, through to the emergence of methodologies suitable for routine laboratory use, followed by the development of professional use, point of care technologies. Finally, the current status of selective tests for cholesterol based on biosensor methodologies is reviewed and the potential for application in consumer diagnostics is discussed. © 2013 The Royal Society of Chemistry

The use of fasting vs. non-fasting triglyceride concentration for estimating the prevalence of high LDL-cholesterol and metabolic syndrome in population surveys

<p>Abstract</p> <p>Background</p> <p>For practical reasons it is not easy to obtain fasting samples in large population health surveys. Non-fasting triglyceride (Tg) values are difficult to interpret. The authors compared the accuracy of statistically corrected non-fasting Tg values with true fasting values and estimated the misclassification of subjects with high low-density lipoprotein cholesterol (LDL-C) and the metabolic syndrome.</p> <p>Methods</p> <p>Non-fasting blood was obtained from a population-based sample of 4282 individuals aged 24-75 years in the National FINRISK 2007 Study. Fasting blood samples were drawn from the same persons 3 months later. Non-fasting serum Tg values were converted into fasting values using previously published formula. LDL-C was calculated and classification of the metabolic syndrome was carried out according to three different latest guidelines.</p> <p>Results</p> <p>The median (25^th, 75th percentile) non-fasting serum Tg concentration was 1.18 (0.87, 1.72) mmol/L and after postprandial correction 1.06 (0.78, 1.52) mmol/L. The true-fasting serum Tg concentration was 1.00 (0.75, 1.38) mmol/L (<it>P </it>< 0.001) vs. non-fasting and corrected value. Bias of the corrected value was +5.9% compared with the true-fasting Tg. Of the true fasting subjects, 56.4% had LDL-C ≥3.00 mmol/L. When calculated using non-fasting serum Tg, the prevalence of high LDL-C was 51.3% and using statistically corrected Tg it was 54.8%. The prevalence of metabolic syndrome was 35.5% among fully fasted persons and among non-fasting subjects 39.7%, which after statistical correction of Tg decreased to 37.6% (P < 0.001 for all comparisons).</p> <p>Conclusions</p> <p>Correction of non-fasting serum Tg to fasting values plays a minor role in population studies but nevertheless reduces misclassification of calculated high LDL-C from 5.1 to 1.6% and the metabolic syndrome from 4.2 to 2.1%.</p

A biosensor for the determination of high density lipoprotein cholesterol employing combined surfactant-derived selectivity and sensitivity enhancements

High density lipoprotein cholesterol (HDL-C) is a modifiable risk factor in cardiovascular disease and devices suitable for its determination at the point of care are critical to the future management of hypercholesterolaemia. An electrochemical biosensor for measuring HDL-C was developed. The biosensor was based on a homogeneous assay methodology for selective determination of HDL-C in combination with a printed electrochemical sensor for measuring the reduction of hydrogen peroxide at a silver paste electrode. The polyoxyethylene alkylene tribenzylphenyl ether surfactant (Emulgen B-66) was found to be capable of both the selective dissolution of HDL particles, as well as the enhanced electrocatalytic reduction of hydrogen peroxide. The resulting biosensor was shown to have a linear response to HDL-C from 0.5 to 4 mM (r2=0.998) with an average r.s.d. of 7%. The biosensor was also used to analyse HDL-C in thirteen serum samples and had good agreement with a commercial spectrophotometric precipitation-based assay (r=0.7222; p < 0.058)

The Effects of Apolipoprotein F Deficiency on High Density Lipoprotein Cholesterol Metabolism in Mice

Apolipoprotein F (apoF) is 29 kilodalton secreted sialoglycoprotein that resides on the HDL and LDL fractions of human plasma. Human ApoF is also known as Lipid Transfer Inhibitor protein (LTIP) based on its ability to inhibit cholesteryl ester transfer protein (CETP)-mediated transfer events between lipoproteins. In contrast to other apolipoproteins, ApoF is predicted to lack strong amphipathic alpha helices and its true physiological function remains unknown. We previously showed that overexpression of Apolipoprotein F in mice reduced HDL cholesterol levels by 20–25% by accelerating clearance from the circulation. In order to investigate the effect of physiological levels of ApoF expression on HDL cholesterol metabolism, we generated ApoF deficient mice. Unexpectedly, deletion of ApoF had no substantial impact on plasma lipid concentrations, HDL size, lipid or protein composition. Sex-specific differences were observed in hepatic cholesterol content as well as serum cholesterol efflux capacity. Female ApoF KO mice had increased liver cholesteryl ester content relative to wild type controls on a chow diet (KO: 3.4+/−0.9 mg/dl vs. WT: 1.2+/−0.3 mg/dl, p<0.05). No differences were observed in ABCG1-mediated cholesterol efflux capacity in either sex. Interestingly, ApoB-depleted serum from male KO mice was less effective at promoting ABCA1-mediated cholesterol efflux from J774 macrophages relative to WT controls

Vicrostatin – An Anti-Invasive Multi-Integrin Targeting Chimeric Disintegrin with Tumor Anti-Angiogenic and Pro-Apoptotic Activities

Similar to other integrin-targeting strategies, disintegrins have previously shown good efficacy in animal cancer models with favorable pharmacological attributes and translational potential. Nonetheless, these polypeptides are notoriously difficult to produce recombinantly due to their particular structure requiring the correct pairing of multiple disulfide bonds for biological activity. Here, we show that a sequence-engineered disintegrin (called vicrostatin or VCN) can be reliably produced in large scale amounts directly in the oxidative cytoplasm of Origami B E. coli. Through multiple integrin ligation (i.e., αvβ3, αvβ5, and α5β1), VCN targets both endothelial and cancer cells significantly inhibiting their motility through a reconstituted basement membrane. Interestingly, in a manner distinct from other integrin ligands but reminiscent of some ECM-derived endogenous anti-angiogenic fragments previously described in the literature, VCN profoundly disrupts the actin cytoskeleton of endothelial cells (EC) inducing a rapid disassembly of stress fibers and actin reorganization, ultimately interfering with EC's ability to invade and form tubes (tubulogenesis). Moreover, here we show for the first time that the addition of a disintegrin to tubulogenic EC sandwiched in vitro between two Matrigel layers negatively impacts their survival despite the presence of abundant haptotactic cues. A liposomal formulation of VCN (LVCN) was further evaluated in vivo in two animal cancer models with different growth characteristics. Our data demonstrate that LVCN is well tolerated while exerting a significant delay in tumor growth and an increase in the survival of treated animals. These results can be partially explained by potent tumor anti-angiogenic and pro-apoptotic effects induced by LVCN