Actin cytoskeleton assembly regulates collagen production via TGF‐β type II receptor in human skin fibroblasts

The dermal compartment of skin is primarily composed of collagen‐rich extracellular matrix (ECM), which is produced by dermal fibroblasts. In Young skin, fibroblasts attach to the ECM through integrins. During ageing, fragmentation of the dermal ECM limits fibroblast attachment. This reduced attachment is associated with decreased collagen production, a major cause of skin thinning and fragility, in the elderly. Fibroblast attachment promotes assembly of the cellular actin cytoskeleton, which generates mechanical forces needed for structural support. The mechanism(s) linking reduced assembly of the actin cytoskeleton to decreased collagen production remains unclear. Here, we report that disassembly of the actin cytoskeleton results in impairment of TGF‐β pathway, which controls collagen production, in dermal fibroblasts. Cytoskeleton disassembly rapidly down‐regulates TGF‐β type II receptor (TβRII) levels. This down‐regulation leads to reduced activation of downstream effectors Smad2/Smad3 and CCN2, resulting in decreased collagen production. These responses are fully reversible; restoration of actin cytoskeleton assembly up‐regulates TβRII, Smad2/Smad3, CCN2 and collagen expression. Finally, actin cytoskeleton‐dependent reduction of TβRII is mediated by induction of microRNA 21, a potent inhibitor of TβRII protein expression. Our findings reveal a novel mechanism that links actin cytoskeleton assembly and collagen expression in dermal fibroblasts. This mechanism likely contributes to loss of TβRII and collagen production, which are observed in aged human skin.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/145494/1/jcmm13685_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/145494/2/jcmm13685-sup-0001-FigS1-S2.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/145494/3/jcmm13685.pd

Regional Medical Campuses: A New Classification System

There is burgeoning belief that regional medical campuses (RMCs) are a significant part of the narrative about medical education and the health care workforce in the United States and Canada. Although RMCs are not new, in the recent years of medical education enrollment expansion, they have seen their numbers increase. Class expansion explains the rapid growth of RMCs in the past 10 years, but it does not adequately describe their function. Often, RMCs have missions that differ from their main campus, especially in the areas of rural and community medicine. The absence of an easy-to-use classification system has led to a lack of current research about RMCs as evidenced by the small number of articles in the current literature. The authors describe the process of the Group on Regional Medical Campuses used to develop attributes of a campus separate from the main campus that constitute a “classification” of a campus as an RMC. The system is broken into four models—basic science, clinical, longitudinal, and combined—and is linked to Liaison Committee on Medical Education standards. It is applicable to all schools and can be applied by any medical school dean or medical education researcher. The classification system paves the way for stakeholders to agree on a denominator of RMCs and conduct future research about their impact on medical education

Training Students on the Effective Use of Translator Services: How Can You Treat Someone You Don’t Understand?

In 2005, the Virginia Commonwealth University School of Medicine partnered with the Inova Health System to create the first regional branch medical campus in Northern Virginia. As a part of this partnership, the VCU School of Medicine Inova Campus accepts a minimum of twenty-four medical students from the third and fourth year classes annually. In an effort to better prepare the incoming students for their clinical years and an extremely diverse patient population, a video was created to demonstrate effective use of translator services

The Medical Futures Program: How One Regional Medical Campus Educates Its Community

Poster created for the 2012 GRMC Session of the AAMC Annual Meeting. The Virginia Commonwealth University School of Medicine Inova Campus has extensive ties to the northern Virginia community. The Medical Futures Program was created to provide valuable information regarding medical school admissions and current physician workforce issues to high school and university students, their parents, and guests

M3 SOAP Note Training: Don’t Take the Basics for Granted

The Virginia Commonwealth University School of Medicine (VCU SOM) is a premier academic medical center in the United States that is focused on medical education innovation. The main campus is located in Richmond, Virginia. In 2005, the VCU SOM partnered with Inova Health Systems to create a regional medical campus in Northern Virginia, the VCU SOM Inova Campus. In August 2009, two fourth-year medical students created and presented on “SOAP Notes: A M3 Primer” to third year students at the Clinical Skills Day, as part of M3 orientation. This project was completed in collaboration with Inova Research in Medical Education Center

Regional Medical Campus Match Data 2007-2009 Comparisons, Analysis, and Trends

Poster created for the 2010 AAMC Workforce Conference, present analysis of match data from all regional medical campuses for 2007-2009

Characteristics of Inflammatory Bowel Disease Serology in Patients With Indeterminate Colitis

Goals and Background Inflammatory bowel disease (IBD) serology testing is often used in patients with indeterminate colitis (IC) to help distinguish between ulcerative colitis (UC) and Crohn’s disease (CD). We investigated the performance of serology testing in predicting future diagnosis in this setting. Study Observational study of individuals with IC at a single center who underwent IBD serology testing (pANCA, ASCA and anti-OmpC) and had at least 12 months follow-up from time of serology result. Results 117 individuals with IC and 1 year follow-up data were enrolled. All IC patients had endoscopic and histologic evidence of colitis at enrollment. One year after serology testing, 58 (50%) individuals with IC were diagnosed with UC, 49 (42%) with CD, and 10 (9%) remained labeled with IC. The sensitivity/specificity of an initial positive pANCA for a subsequent diagnosis of UC was 78%/44%. For ASCA and anti-OmpC, the results were 18%/84% and 27%/75%, respectively, for a subsequent diagnosis of CD. A positive pANCA test was associated with a likelihood ratio (LR) of 1.4 (95% CI: 1.1–1.8) for a subsequent diagnosis of UC at 1 year. Neither positive ASCA (LR 1.1; 95% CI: 0.5–2.5) nor anti-OmpC (LR 1.1; 95% CI: 0.6–2.0) was associated with a subsequent diagnosis CD in patients with IC. Conclusions The disease phenotype in the majority of individuals initially labeled with IC evolved to be more consistent with either UC or CD on follow-up. pANCA, ASCA, and anti-OmpC, individually, were of limited utility in predicting a patient’s subsequent disease phenotype

Ideal magnetohydrodynamic simulations of unmagnetized dense plasma jet injection into a hot strongly magnetized plasma

We present results from three-dimensional ideal magnetohydrodynamic simulations of unmagnetized dense plasma jet injection into a uniform hot strongly magnetized plasma, with the aim of providing insight into core fueling of a tokamak with parameters relevant for ITER and NSTX (National Spherical Torus Experiment). Unmagnetized dense plasma jet injection is similar to compact toroid injection but with much higher plasma density and total mass, and consequently lower required injection velocity. Mass deposition of the jet into the background appears to be facilitated via magnetic reconnection along the jet's trailing edge. The penetration depth of the plasma jet into the background plasma is mostly dependent on the jet's initial kinetic energy, and a key requirement for spatially localized mass deposition is for the jet's slowing-down time to be less than the time for the perturbed background magnetic flux to relax due to magnetic reconnection. This work suggests that more accurate treatment of reconnection is needed to fully model this problem. Parameters for unmagnetized dense plasma jet injection are identified for localized core deposition as well as edge localized mode (ELM) pacing applications in ITER and NSTX-relevant regimes.Comment: 16 pages, 8 figures and 2 tables; accepted by Nuclear Fusion (May 11, 2011

The Burden of Inflammatory Bowel Disease: A Patient-Reported Qualitative Analysis and Development of a Conceptual Model

Background The aim of this study was to describe the impacts of inflammatory bowel disease (IBD) from the patients’ perspective, and to inform the development of a conceptual model. Methods Focus groups and one-on-one interviews were undertaken in adult patients with IBD. Transcripts from the focus groups and interviews were analyzed to identify themes and links between themes, assisted by qualitative data software MaxQDA. Themes from the qualitative research were supplemented with those reported in the literature and concepts included in IBD-specific patient-reported outcome (PRO) measures. Results Twenty-seven patients participated. Key physical symptoms included pain, bowel-related symptoms such as frequency, urgency, incontinence, diarrhea, passing blood, and systemic symptoms such as weight loss and fatigue. Participants described continuing and variable symptom experiences. IBD symptoms caused immediate disruption of activities but also had ongoing impacts on daily activities, including dietary restrictions, lifestyle changes, and maintaining close proximity to a toilet. More distal impacts included interference with work, school, parenting, social and leisure activities, relationships, and psychological well-being. The inconvenience of rectal medications, refrigerated biologics, and medication refills emerged as novel burdens not identified in existing PRO measures. Conclusions IBD symptoms cause immediate disruption in activities, but patients may continue to experience some symptoms on a chronic basis. The conceptual model presented here may be useful for identifying target concepts for measurement in future studies in IBD