Implant healing in experimental animal models of diabetes.

Diabetes mellitus is becoming increasingly prevalent worldwide. Additionally, there is an increasing number of patients receiving implantable devices such as glucose sensors and orthopedic implants. Thus, it is likely that the number of diabetic patients receiving these devices will also increase. Even though implantable medical devices are considered biocompatible by the Food and Drug Administration, the adverse tissue healing that occurs adjacent to these foreign objects is a leading cause of their failure. This foreign body response leads to fibrosis, encapsulation of the device, and a reduction or cessation of device performance. A second adverse event is microbial infection of implanted devices, which can lead to persistent local and systemic infections and also exacerbates the fibrotic response. Nearly half of all nosocomial infections are associated with the presence of an indwelling medical device. Events associated with both the foreign body response and implant infection can necessitate device removal and may lead to amputation, which is associated with significant morbidity and cost. Diabetes mellitus is generally indicated as a risk factor for the infection of a variety of implants such as prosthetic joints, pacemakers, implantable cardioverter defibrillators, penile implants, and urinary catheters. Implant infection rates in diabetic patients vary depending upon the implant and the microorganism, however, for example, diabetes was found to be a significant variable associated with a nearly 7.2% infection rate for implantable cardioverter defibrillators by the microorganism Candida albicans. While research has elucidated many of the altered mechanisms of diabetic cutaneous wound healing, the internal healing adjacent to indwelling medical devices in a diabetic model has rarely been studied. Understanding this healing process is crucial to facilitating improved device design. The purpose of this article is to summarize the physiologic factors that influence wound healing and infection in diabetic patients, to review research concerning diabetes and biomedical implants and device infection, and to critically analyze which diabetic animal model might be advantageous for assessing internal healing adjacent to implanted devices

Characterization of porous, dexamethasone-releasing polyurethane coatings for glucose sensors.

Commercially available implantable needle-type glucose sensors for diabetes management are robust analytically but can be unreliable clinically primarily due to tissue-sensor interactions. Here, we present the physical, drug release and bioactivity characterization of tubular, porous dexamethasone (Dex)-releasing polyurethane coatings designed to attenuate local inflammation at the tissue-sensor interface. Porous polyurethane coatings were produced by the salt-leaching/gas-foaming method. Scanning electron microscopy and micro-computed tomography (micro-CT) showed controlled porosity and coating thickness. In vitro drug release from coatings monitored over 2 weeks presented an initial fast release followed by a slower release. Total release from coatings was highly dependent on initial drug loading amount. Functional in vitro testing of glucose sensors deployed with porous coatings against glucose standards demonstrated that highly porous coatings minimally affected signal strength and response rate. Bioactivity of the released drug was determined by monitoring Dex-mediated, dose-dependent apoptosis of human peripheral blood derived monocytes in culture. Acute animal studies were used to determine the appropriate Dex payload for the implanted porous coatings. Pilot short-term animal studies showed that Dex released from porous coatings implanted in rat subcutis attenuated the initial inflammatory response to sensor implantation. These results suggest that deploying sensors with the porous, Dex-releasing coatings is a promising strategy to improve glucose sensor performance

Laminar flow of two miscible fluids in a simple network

When a fluid comprised of multiple phases or constituents flows through a network, non-linear phenomena such as multiple stable equilibrium states and spontaneous oscillations can occur. Such behavior has been observed or predicted in a number of networks including the flow of blood through the microcirculation, the flow of picoliter droplets through microfluidic devices, the flow of magma through lava tubes, and two-phase flow in refrigeration systems. While the existence of non-linear phenomena in a network with many inter-connections containing fluids with complex rheology may seem unsurprising, this paper demonstrates that even simple networks containing Newtonian fluids in laminar flow can demonstrate multiple equilibria. The paper describes a theoretical and experimental investigation of the laminar flow of two miscible Newtonian fluids of different density and viscosity through a simple network. The fluids stratify due to gravity and remain as nearly distinct phases with some mixing occurring only by diffusion. This fluid system has the advantage that it is easily controlled and modeled, yet contains the key ingredients for network non-linearities. Experiments and 3D simulations are first used to explore how phases distribute at a single T-junction. Once the phase separation at a single junction is known, a network model is developed which predicts multiple equilibria in the simplest of networks. The existence of multiple stable equilibria is confirmed experimentally and a criteria for their existence is developed. The network results are generic and could be applied to or found in different physical systems

Legal guardians understand how children with the human immunodeficiency virus perceive quality of life and stigma

AIM: This aim of this study was to describe how legal guardians assessed health-related quality of life and HIV-related stigma in children with the human immunodeficiency virus (HIV) compared to the children's own ratings. METHODS: A cross-sectional nationwide study was performed to compare how 37 children aged from eight to 16 years of age with perinatal HIV, and their legal guardians, assessed the children's health-related quality of life and HIV-related stigma. Data were collected using the 37-item DISABKIDS Chronic Generic Module and a short eight-item version of the HIV stigma scale. RESULTS: Intraclass correlations indicated concordance between the legal guardians' ratings and the children's own ratings of the child's health-related quality of life and HIV-related stigma. There were no statistically significant differences between the ratings of the two groups and gender did not have any impact on the results. Both groups indicated that the children had concerns about being open about their HIV status. CONCLUSION: The results of this study indicated that legal guardians understood how their children perceived their health-related quality of life and HIV-related stigma. The results also indicated the need for interventions to support both the children and legal guardians when it came to disclosing the child's HIV status

Detecting, Preventing, and Responding to “Fraudsters” in Internet Research: Ethics and Tradeoffs

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/111094/1/jlme12200.pd

Living with ‘melanoma’…for a day: a phenomenological analysis of medical students’ simulated experiences

Background Despite the rising incidence of melanoma, medical students have progressively fewer opportunities to encounter patients with this important condition. Curricula tend to attach the greatest value to intellectual forms of learning. Compared to intellectual learning, however, experiential learning affords students deep insights about a condition. Doctors who experience ill health are more empathic towards patients. However opportunities to learn about cancer experientially are limited. Temporary transfer tattoos can simulate the ill health associated with melanoma. We reasoned that, if doctors who have been sick are more empathic, temporarily ‘having’ melanoma might have a similar effect. Objectives Explore the impact of wearing a melanoma tattoo on medical students’ understanding of patienthood and attitudes towards patients with melanoma. Methods Ten fourth year medical students were recruited to a simulation. They wore a melanoma tattoo for 24 hours and listened to a patient’s account of receiving their diagnosis. Data were captured using audio-diaries and face-to-face interviews, transcribed, and analysed phenomenologically using the template analysis method. Results There were four themes: 1) Melanoma simulation: opening up new experiences; 2) Drawing upon past experiences; 3) A transformative introduction to patienthood; 4) Doctors in the making: seeing cancer patients in a new light. Conclusions By means of a novel simulation, medical students were introduced to lived experiences of having a melanoma. Such an inexpensive simulation can prompt students to reflect critically on the empathetic care of such patients in the future

How IRBs View and Make Decisions about Social Risks

Whether and how irbs assess social risks remains unclear, with little empirical investigation. I contacted leaders of 60 IRBs, and interviewed IRB leaders from 34 (response rate = 55%) and additionally, 12 members and administrators. IRBs struggle to assess and balance social risks and benefits, and vary in whether, how, and how much to do so, and how to balance these against individual risks/benefits. Risks to a group affect individuals within it. Hence, social risks can include indirect individual risks, raising ambiguities. Dilemmas emerge: E.g., how much responsibility researchers and IRBs have for addressing broader health inequities. These data, the first to examine how IRBs make decisions about social risks, reveal how IRBs face critical challenges, dilemmas, and ambiguities

Consenting for Molecular Diagnostics

The growing use of molecular diagnostics poses a wide range of issues and questions concerning informed consent that researchers, health care providers, and others will increasingly need to address. Molecular diagnostics are advancing more rapidly than our ability to decide how best to respond to their complex medical, ethical, legal, psychological, and social implications. Although some of these issues resemble those posed by prior tests, the newness and ever-faster spread of these tests, the advent of large-scale electronic databases, and the many inherent uncertainties involved present new challenges and dilemmas that require careful attention to determine how best to proceed. Obtaining appropriate informed consent will require considerable resources, which many researchers and providers may not fully appreciate. For example, for whole genome sequencing (WGS)2 and whole exome sequencing (WES), most researchers have indicated that they were willing to spend 30 minutes or less on obtaining informed consent (1). Yet the complexity of the information involved will probably often require significantly longer interactions