Monitoring Vascular Permeability and Remodeling After Endothelial Injury in a Murine Model Using a Magnetic Resonance Albumin-Binding Contrast Agent

Background-Despite the beneficial effects of vascular interventions, these procedures may damage the endothelium leading to increased vascular permeability and remodeling. Re-endothelialization of the vessel wall, with functionally and structurally intact cells, is controlled by endothelial nitric oxide synthase (NOS3) and is crucial for attenuating adverse effects after injury. We investigated the applicability of the albumin-binding MR contrast agent, gadofosveset, to noninvasively monitor focal changes in vascular permeability and remodeling, after injury, in NOS3-knockout (NOS3(-/-)) and wild-type (WT) mice in vivo.Methods and Results-WT and NOS3(-/-) mice were imaged at 7, 15, and 30 days after aortic denudation or sham-surgery. T-1 mapping (R-1=1/T-1, s(-1)) and delayed-enhanced MRI were used as measurements of vascular permeability (R-1) and remodeling (vessel wall enhancement, mm(2)) after gadofosveset injection, respectively. Denudation resulted in higher vascular permeability and vessel wall enhancement 7 days after injury in both strains compared with sham-operated animals. However, impaired re-endothelialization and increased neovascularization in NOS3(-/-) mice resulted in significantly higher R-1 at 15 and 30 days post injury compared with WT mice that showed re-endothelialization and lack of neovascularization (R-1 [s(-1)]=15 days: (-/-)(NOS3)4.02 [interquartile range, IQR, 3.77-4.41] versus (WT)2.39 [IQR, 2.35-2.92]; 30 days: (-/-)(NOS3)4.23 [IQR, 3.94-4.68] versus (WT)2.64 [IQR, 2.33-2.80]). Similarly, vessel wall enhancement was higher in NOS3(-/-) but recovered in WT mice (area [mm(2)]=15 days: (-/-)(NOS3)5.20 [IQR, 4.68-6.80] versus (WT)2.13 [IQR, 0.97-3.31]; 30 days: (-/-)(NOS3)7.35 [IQR, 5.66-8.61] versus (WT)1.60 [IQR, 1.40-3.18]). Ex vivo histological studies corroborated the MRI findings.Conclusions-We demonstrate that increased vascular permeability and remodeling, after injury, can be assessed noninvasively using an albumin-binding MR contrast agent and may be used as surrogate markers for evaluating the healing response of the vessel wall after injury.</p

The Association of Patient Factors, Digital Access, and Online Behavior on Sustained Patient Portal Use: A Prospective Cohort of Enrolled Users

BACKGROUND: As electronic health records and computerized workflows expand, there are unprecedented opportunities to digitally connect with patients using secure portals. To realize the value of patient portals, initial reach across populations will need to be demonstrated, as well as sustained usage over time. OBJECTIVE: The study aim was to identify patient factors associated with short-term and long-term portal usage after patients registered to access all portal functions. METHODS: We prospectively followed a cohort of patients at a large Department of Veterans Affairs (VA) health care facility who recently completed identity proofing to use the VA patient portal. Information collected at baseline encompassed patient factors potentially associated with portal usage, including: demographics, Internet access and use, health literacy, patient activation, and self-reported health conditions. The primary outcome was the frequency of portal log-ins during 6-month and 18-month time intervals after study enrollment. RESULTS: A total of 270 study participants were followed prospectively. Almost all participants (260/268, 97.0%) reported going online, typically at home (248/268, 92.5%). At 6 months, 84.1% (227/270) of participants had visited the portal, with some variation in usage across demographic and health-related subgroups. There were no significant differences in portal log-ins by age, gender, education, marital status, race/ethnicity, distance to a VA facility, or patient activation measure. Significantly higher portal usage was seen among participants using high-speed broadband at home, greater self-reported ability using the Internet, and routinely going online. By 18 months, 91% participants had logged in to the portal, and no significant associations were found between usage and demographics, health status, or patient activation. When examining portal activity between 6 and 18 months, patients who were infrequent or high portal users remained in those categories, respectively. CONCLUSIONS: Short-term and long-term portal usage was associated with having broadband at home, high self-rated ability when using the Internet, and overall online behavior. Digital inclusion, or ready access to the Internet and digital skills, appears to be a social determinant in patient exposure to portal services

Stress from Uncertainty from Graduation to Retirement—A Population-Based Study of Swiss Physicians

BACKGROUND: Uncertainty shapes many decisions made by physicians everyday. Uncertainty and physicians’ inability to handle it may result in substandard care and unexplained variations in patterns of care. OBJECTIVE: To describe socio-demographic and professional characteristics of reactions to uncertainty among physicians from all specialties, including physicians in training. DESIGN: Cross-sectional postal survey. PARTICIPANT: All physicians practicing in Geneva, Switzerland (n = 1,994). MEASUREMENT: Reaction to medical care uncertainty was measured with the Anxiety Due to Uncertainty and Concern About Bad Outcomes scales. The questionnaire also included items about professional characteristics and work-related satisfaction scales. RESULTS: After the first mailing and two reminders, 1,184 physicians responded to the survey. In univariate analysis, women, junior physicians, surgical specialists, generalist physicians, and physicians with lower workloads had higher scores in both scales. In multivariate models, sex, medical specialty, and workload remained significantly associated with both scales, whereas clinical experience remained associated only with concern about bad outcomes. Higher levels of anxiety due to uncertainty were associated with lower scores of work-related satisfaction, while higher levels of concern about bad outcomes were associated with lower satisfaction scores for patient care, personal rewards, professional relations, and general satisfaction, but not for work-related burden or satisfaction with income-prestige. The negative effect of anxiety due to uncertainty on work-related satisfaction was more important for physicians in training. CONCLUSION: Physicians’ reactions to uncertainty in medical care were associated with several dimensions of work-related satisfaction. Physicians in training experienced the greatest impact of anxiety due to uncertainty on their work-related satisfaction. Incorporating strategies to deal with uncertainty into residency training may be useful

A review of clinical decision-making: Models and current research

Aims and objectives: The aim of this paper was to review the current literature with respect to clinical decision-making models and the educational application of models to clinical practice. This was achieved by exploring the function and related research of the three available models of clinical decision making: information processing model, the intuitive-humanist model and the clinical decision making model. Background: Clinical decision-making is a unique process that involves the interplay between knowledge of pre-existing pathological conditions, explicit patient information, nursing care and experiential learning. Historically, two models of clinical decision making are recognised from the literature; the information processing model and the intuitive-humanist model. The usefulness and application of both models has been examined in relation the provision of nursing care and care related outcomes. More recently a third model of clinical decision making has been proposed. This new multidimensional model contains elements of the information processing model but also examines patient specific elements that are necessary for cue and pattern recognition. Design: Literature review Methods: Evaluation of the literature generated from MEDLINE, CINAHL, OVID, PUBMED and EBESCO systems and the Internet from 1980 – November 2005

The GAPS Experiment to Search for Dark Matter using Low-energy Antimatter

The GAPS experiment is designed to carry out a sensitive dark matter search by measuring low-energy cosmic ray antideuterons and antiprotons. GAPS will provide a new avenue to access a wide range of dark matter models and masses that is complementary to direct detection techniques, collider experiments and other indirect detection techniques. Well-motivated theories beyond the Standard Model contain viable dark matter candidates which could lead to a detectable signal of antideuterons resulting from the annihilation or decay of dark matter particles. The dark matter contribution to the antideuteron flux is believed to be especially large at low energies (E < 1 GeV), where the predicted flux from conventional astrophysical sources (i.e. from secondary interactions of cosmic rays) is very low. The GAPS low-energy antiproton search will provide stringent constraints on less than 10 GeV dark matter, will provide the best limits on primordial black hole evaporation on Galactic length scales, and will explore new discovery space in cosmic ray physics. Unlike other antimatter search experiments such as BESS and AMS that use magnetic spectrometers, GAPS detects antideuterons and antiprotons using an exotic atom technique. This technique, and its unique event topology, will give GAPS a nearly background-free detection capability that is critical in a rare-event search. GAPS is designed to carry out its science program using long-duration balloon flights in Antarctica. A prototype instrument was successfully flown from Taiki, Japan in 2012. GAPS has now been approved by NASA to proceed towards the full science instrument, with the possibility of a first long-duration balloon flight in late 2020. Here we motivate low-energy cosmic ray antimatter searches and discuss the current status of the GAPS experiment and the design of the payload.Comment: 8 pags, 3 figures, Proc. 35th International Cosmic Ray Conference (ICRC 2017), Busan, Kore

Targeting mitochondrial 18 kDa translocator protein (TSPO) regulates macrophage cholesterol efflux and lipid phenotype

Abstract The aim of the present study was to establish mitochondrial cholesterol trafficking 18 kDa translocator protein (TSPO) as a potential therapeutic target, capable of increasing macrophage cholesterol efflux to (apo)lipoprotein acceptors. Expression and activity of TSPO in human (THP-1) macrophages were manipulated genetically and by the use of selective TSPO ligands