In Vivo Analysis Of Angiotensin II-Induced Hypertension And Vascular Disease In Rats

Murine models of abdominal aortic aneurysms (AAA) are commonly used to study the pathogenesis of this disease. Rats are often used in laboratory studies because of their size and because they are more physiologically similar to humans than mice are. In this study, we subcutaneously implanted 9-week-old apolipoprotein E-deficient (apoE KO) rats with angiotensin II-filled pumps to study the effects of this vasoconstricting hormone on aneurysm development. Deletion of the apoE gene in mice causes excess lipid accumulation in the blood vessels, thereby increasing the likelihood of atherosclerotic lesions in the aorta. However, atherosclerotic plaque buildup was not evident when the rats consumed either normal chow or high fat diets, and no dissecting aneurysms were identified via ultrasound. We observed an average of 32.5 +/- 28.8 mmHg increase in systolic blood pressures as early as 4 days post-pump implantation and an increase of 54.2 +/- 25.9 mmHg from baseline 6 weeks after angiotensin II infusion began. This study shows that apoE KO rats can be valuable models for the physiological development of hypertension but not for dissecting suprarenal aneurysms. Future studies will focus on studying the effects of angiotensin II on the hearts of these genetically modified animals

The Joint Efficient Dark-energy Investigation (JEDI): Measuring the cosmic expansion history from type Ia supernovae

JEDI (Joint Efficient Dark-energy Investigation) is a candidate implementation of the NASA-DOE Joint Dark Energy Mission (JDEM). JEDI will probe dark energy in three independent methods: (1) type Ia supernovae, (2) baryon acoustic oscillations, and (3) weak gravitational lensing. In an accompanying paper, an overall summary of the JEDI mission is given. In this paper, we present further details of the supernova component of JEDI. To derive model-independent constraints on dark energy, it is important to precisely measure the cosmic expansion history, H(z), in continuous redshift bins from z \~ 0-2 (the redshift range in which dark energy is important). SNe Ia at z > 1 are not readily accessible from the ground because the bulk of their light has shifted into the near-infrared where the sky background is overwhelming; hence a space mission is required to probe dark energy using SNe. Because of its unique near-infrared wavelength coverage (0.8-4.2 microns), JEDI has the advantage of observing SNe Ia in the rest frame J band for the entire redshift range of 0 < z < 2, where they are less affected by dust, and appear to be nearly perfect standard candles. During the first year of JEDI operations, spectra and light curves will be obtained for ~4,000 SNe Ia at z < 2. The resulting constraints on dark energy are discussed, with special emphasis on the improved precision afforded by the rest frame near-infrared data.Comment: 8 pages, accepted for publication in SPIE proceeding

Changes in Vessel Properties During Early Progression of Murine Abdominal Aortic Aneurysms from In Vivo Ultrasound

Abdominal aortic aneurysms (AAA) are a common and frequently fatal disease characterized by the weakening and dilation of the aorta. The larger the aneurysm, the higher the chances are of rupturing and life-threatening hemorrhage. The aim of this study is to apply the angiotensin II (AngII) model of AAAs in male apolipoprotein-E-deficient mice (apoE-/- C57Bl/6J), in order to analyze, quantify, and understand the pathologies and characteristics associated with early AAA development. To date, many studies focusing on the evaluation of AAA characteristics have been performed ex vivo. Therefore, we focused on in vivo assessment, through the use of high frequency ultrasound technology, to measure parameters such as aortic diameter, volume, circumferential cyclic strain, blood flow velocity, and thrombus volume. Data analysis from this 7-day study suggests an increase in aortic diameter and volume, a decrease in aortic blood flow velocity and strain, and large variations in volumes of the thrombotic volume within the aneurysm’s false lumen. Our analysis of these AAA features has shown that there are a variety of patterns, which may provide insight into further understanding AAA pathology in this model. Future work will focus on comparing the relationship between the features during early AAA formation

User-centred design using Gamestorming

© 2016 IMIA and IOS Press. User-centered design (UX) is becoming a standard in software engineering and has tremendous potential in healthcare. The purpose of this tutorial will be to demonstrate and provide participants with practice in usercentred design methods that involve 'Gamestorming', a form of brainstorming where 'the rules of life are temporarily suspended'. Participants will learn and apply gamestorming methods including persona development via empathy mapping and methods to translate artefacts derived from participatory design sessions into functional and design requirements

Catalytic Isohypsic-Redox Sequences for the Rapid Generation of C_sp3-Containing Heterocycles

Cross‐coupling reactions catalyzed by transition metals are among the most influential in modern synthetic chemistry. The vast majority of transition metal catalyzed cross‐couplings rely on a catalytic cycle involving alternating oxidation and reduction of the metal center and are generally limited to forging just one type of new bond per reaction (e.g. the biaryl linkage formed during a Suzuki cross‐coupling). Here we present an Isohypsic–Redox Sequence (IRS) that uses one metal to effect two catalytic cycles, thereby generating multiple new types of bonds from a single catalyst source. We show that the IRS strategy is amenable to several widely used transformations including the Suzuki–Miyaura coupling, Buchwald–Hartwig amination, and Wacker oxidation. Furthermore, each of these reactions generates value‐added heterocycles with significant sp3‐C (3‐dimensional) content. Our results provide a general framework for generating complex products by using a single metal to fulfill multiple roles. By uniting different combinations of reactions in the isohypsic and redox phases of the process, this type of catalytic multiple bond‐forming platform has the potential for wide applicability in the efficient synthesis of functional organic molecules

Revealing nascent proteomics in signaling pathways and cell differentiation.

Regulation of gene expression at the level of protein synthesis is a crucial element in driving how the genetic landscape is expressed. However, we are still limited in technologies that can quantitatively capture the immediate proteomic changes that allow cells to respond to specific stimuli. Here, we present a method to capture and identify nascent proteomes in situ across different cell types without disturbing normal growth conditions, using O-propargyl-puromycin (OPP). Cell-permeable OPP rapidly labels nascent elongating polypeptides, which are subsequently conjugated to biotin-azide, using click chemistry, and captured with streptavidin beads, followed by digestion and analysis, using liquid chromatography-tandem mass spectrometry. Our technique of OPP-mediated identification (OPP-ID) allows detection of widespread proteomic changes within a short 2-hour pulse of OPP. We illustrate our technique by recapitulating alterations of proteomic networks induced by a potent mammalian target of rapamycin inhibitor, MLN128. In addition, by employing OPP-ID, we identify more than 2,100 proteins and uncover distinct protein networks underlying early erythroid progenitor and differentiation states not amenable to alternative approaches such as amino acid analog labeling. We present OPP-ID as a method to quantitatively identify nascent proteomes across an array of biological contexts while preserving the subtleties directing signaling in the native cellular environment

The Ursinus Weekly, October 7, 1963

Customs program: Class of 1967 well underway • Sororities begin Fall rushing Wed. • Harpsichordist Temple Painter to be featured in first Forum Wednesday • Dr. Foster on sabbatical • Choral groups begin rehearsals • Y retreat set for Oct. 11 & 12 • Sue Harmon in Mr. Roberts • More than 980 enrolled this Fall • Honors rating to 23 freshmen • UC student named president of SNEA • Students ready to teach; Banquet set for tonight • Editorial: Word of welcome • Danforth graduate fellowships available • Dateline: Stockholm, Sweden • Letters to the editor • Three faculty members receive distinguished teaching award • Record enrollment in Evening School • National Security Agency test • From behind my dink • Oral cultural vaccine given • Class \u2763 ranks top in education • Summer research, study for faculty • Susquehanna mauls Bears in opener, 32-0 • Ursinus host to foreign teams • Williamson named most valuable in MAC Southern div. • Vernon Morgan ends track careerhttps://digitalcommons.ursinus.edu/weekly/1252/thumbnail.jp

Economic evaluation of short treatment for multidrugresistant tuberculosis, Ethiopia and South Africa : the STREAM trial

OBJECTIVE STREAM was a phase-III non-inferiority randomised controlled trial (RCT) to evaluate a shortened regimen for multi-drug resistant tuberculosis (MDR-TB), and included the first-ever within-trial economic evaluation of such regimens, reported here. METHODS We compared the costs of ‘Long’ (20-22 months) and ‘Short’ (9-11 months) regimens in Ethiopia and South Africa. Cost data were collected from trial participants, and health system costs estimated using ‘bottom-up’ and ‘top-down’ costing approaches. A cost-effectiveness analysis was conducted with the trial primary outcome as the measure of effectiveness, including a probabilistic sensitivity analysis (PSA) to illustrate decision uncertainty. FINDINGS The Short-regimen reduced healthcare costs per case by 21% in South Africa (US$8,341 Long vs US$6,619 Short) and 25% in Ethiopia (US$6,097 Long vs US$4,552 Short). The largest component of this saving was medication in South Africa (67%) and social support in Ethiopia (35%). In Ethiopia, participants on the Short-regimen reported reductions in dietary supplementation expenditure (US$225 per case (95$13 (95%CI 11-14), South Africa US$64 (95$19,000 (Ethiopia) or <US$14,500 (South Africa). CONCLUSION The Short-regimen provided substantial health system cost savings and reduced financial burden on participants. Shorter regimens are likely to be cost-effective in most settings, and an effective strategy to support the WHO goal of eliminating catastrophic costs in T

The Relationships Among Social Capital, HIV Self-Management, and Substance Use in Women.

Women living with HIV (WLHIV) face unique challenges to successfully self-manage HIV including substance use and limited social capital. We conducted a 6-month mixed-methods study to describe how social capital influences HIV self-management and substance use among WLHIV. Participants completed a self-report survey and in-depth interview at baseline, and 3 and 6 months. Descriptive statistics, t-tests, and generalized estimating equations (GEEs) were used to examine quantitative relationships. Qualitative data were analyzed using qualitative description. Current substance users reported lower social capital compared with past substance users (2.63 vs. 2.80; p = .34). Over time, substance use and social capital were associated with HIV self-management (Wald χ2 = 28.43; p &lt; .001). Qualitative data suggest that HIV self-management is influenced by overlapping experiences with social capital, including influential trust, community, and value of self can be complicated by ongoing substance use. Social capital can facilitate improved HIV self-management; however, substance use and trauma can weaken this relationship