Transcript of The Dory Derby Accident

This story is an excerpt from a longer interview that was collected as part of the Launching through the Surf: The Dory Fleet of Pacific City project. In this story, Don Grotjohn recounts an accident that occurred during a Dory Derby competition

No evidence for cardiac dysfunction in Kif6 mutant mice.

A KIF6 variant in man has been reported to be associated with adverse cardiovascular outcomes after myocardial infarction. No clear biological or physiological data exist for Kif6. We sought to investigate the impact of a deleterious KIF6 mutation on cardiac function in mice. Kif6 mutant mice were generated and verified. Cardiac function was assessed by serial echocardiography at baseline, after ageing and after exercise. Lipid levels were also measured. No discernable adverse lipid or cardiac phenotype was detected in Kif6 mutant mice. These data suggest that dysfunction of Kif6 is linked to other more complex biological/biochemical parameters or is unlikely to be of material consequence in cardiac function

Strategies to inhibit tumour associated integrin receptors: rationale for dual and multi-antagonists

YesThe integrins are a family of 24 heterodimeric transmembrane cell surface receptors. Involvement in cell attachment to the extracellular matrix, motility, and proliferation identifies integrins as therapeutic targets in cancer and associated conditions; thrombosis, angiogenesis and osteoporosis. The most reported strategy for drug development is synthesis of an agent that is highly selective for a single integrin receptor. However, the ability of cancer cells to change their integrin repertoire in response to drug treatment renders this approach vulnerable to the development of resistance and paradoxical promotion of tumor growth. Here, we review progress towards development of antagonists targeting two or more members of the RGD-binding integrins, notably αvβ3, αvβ5, αvβ6, αvβ8, α5β1, and αIIbβ3, as anticancer therapeutics

The rise of consumer health wearables: promises and barriers

Will consumer wearable technology ever be adopted or accepted by the medical community? Patients and practitioners regularly use digital technology (e.g., thermometers and glucose monitors) to identify and discuss symptoms. In addition, a third of general practitioners in the United Kingdom report that patients arrive with suggestions for treatment based on online search results. However, consumer health wearables are predicted to become the next “Dr Google.” One in six (15%) consumers in the United States currently uses wearable technology, including smartwatches or fitness bands. While 19 million fitness devices are likely to be sold this year, that number is predicted to grow to 110 million in 2018. As the line between consumer health wearables and medical devices begins to blur, it is now possible for a single wearable device to monitor a range of medical risk factors. Potentially, these devices could give patients direct access to personal analytics that can contribute to their health, facilitate preventive care, and aid in the management of ongoing illness. However, how this new wearable technology might best serve medicine remains unclea

The Aberrant Right Subclavian Artery (Arteria Lusoria): The Morphological and Clinical Aspects of One of the Most Important Variations—A Systematic Study of 141 Reports

The most important abnormality of the aortic arch is arguably the presence of an aberrant right subclavian artery (arteria lusoria). If this vessel compresses the adjacent structures, several symptoms may be produced. The aim of the study is to present the morphological and clinical aspects of the aberrant right subclavian artery. Three different databases searched for a review of pertinent literature using strictly predetermined criteria. Of 141 cases, 15 were cadaveric and 126 were clinically documented. The gender distribution of the subjects was 55.3% female and 44.7% male. The mean age of the patients at symptoms onset was 49.9±19.4 years for all patients but 54.0±19.6 years and 44.9±18.1 years for female and male subjects, respectively (P=0.0061). The most common symptoms in this group were dysphagia (71.2%), dyspnea (18.7%), retrosternal pain (17.0%), cough (7.6%), and weight loss (5.9%). The vascular anomalies coexisting with an arteria lusoria were truncus bicaroticus (19.2%), Kommerell’s diverticulum (14.9%), aneurysm of the artery itself (12.8%), and a right sided aortic arch (9.2%). In conclusion, compression of adjacent structures by an aberrant right subclavian artery needs to be differentiated from other conditions presenting dysphagia, dyspnea, retrosternal pain, cough, and weight loss

Myofibroblast-Derived SFRP1 as Potential Inhibitor of Colorectal Carcinoma Field Effect

Epigenetic changes of stromal-epithelial interactions are of key importance in the regulation of colorectal carcinoma (CRC) cells and morphologically normal, but genetically and epigenetically altered epithelium in normal adjacent tumor (NAT) areas. Here we demonstrated retained protein expression of well-known Wnt inhibitor, secreted frizzled-related protein 1 (SFRP1) in stromal myofibroblasts and decreasing epithelial expression from NAT tissues towards the tumor. SFRP1 was unmethylated in laser microdissected myofibroblasts and partially hypermethylated in epithelial cells in these areas. In contrast, we found epigenetically silenced myofibroblast-derived SFRP1 in CRC stroma. Our results suggest that the myofibroblast-derived SFRP1 protein might be a paracrine inhibitor of epithelial proliferation in NAT areas and loss of this signal may support tumor proliferation in CRC

The Intensive Diet and Exercise for Arthritis (IDEA) trial: design and rationale

Background: Obesity is the most modifiable risk factor, and dietary induced weight loss potentially the best nonpharmacologic intervention to prevent or to slow osteoarthritis (OA) disease progression. We are currently conducting a study to test the hypothesis that intensive weight loss will reduce inflammation and joint loads sufficiently to alter disease progression, either with or without exercise. This article describes the intervention, the empirical evidence to support it, and test-retest reliability data. Methods/Design: This is a prospective, single-blind, randomized controlled trial. The study population consists of 450 overweight and obese (BMI = 27-40.5 kg/m2) older (age greater than or equal to 55 yrs) adults with tibiofemoral osteoarthritis. Participants are randomized to one of three 18-month interventions: intensive dietary restriction-plus-exercise; exercise-only; or intensive dietary restriction-only. The primary aims are to compare the effects of these interventions on inflammatory biomarkers and knee joint loads. Secondary aims will examine the effects of these interventions on function, pain, and mobility; the dose response to weight loss on disease progression; if inflammatory biomarkers and knee joint loads are mediators of the interventions; and the association between quadriceps strength and disease progression. Results: Test-retest reliability results indicated that the ICCs for knee joint load variables were excellent, ranging from 0.86 - 0.98. Knee flexion/extension moments were most affected by BMI, with lower reliability with the highest tertile of BMI. The reliability of the semi-quantitative scoring of the knee joint using MRI exceeded previously reported results, ranging from a low of 0.66 for synovitis to a high of 0.99 for bone marrow lesion size. Discussion: The IDEA trial has the potential to enhance our understanding of the OA disease process, refine weight loss and exercise recommendations in this prevalent disease, and reduce the burden of disability. Originally published BMC Musculoskeletal Disorders, Vol. 10, No. 93, July 200

Gremlin-1 Induces BMP-Independent Tumor Cell Proliferation, Migration, and Invasion

Gremlin-1, a bone morphogenetic protein (BMP) antagonist, is overexpressed in various cancerous tissues but its role in carcinogenesis has not been established. Here, we report that gremlin-1 binds various cancer cell lines and this interaction is inhibited by our newly developed gremlin-1 antibody, GRE1. Gremlin-1 binding to cancer cells was unaffected by the presence of BMP-2, BMP-4, and BMP-7. In addition, the binding was independent of vascular endothelial growth factor receptor-2 (VEGFR2) expression on the cell surface. Addition of gremlin-1 to A549 cells induced a fibroblast-like morphology and decreased E-cadherin expression. In a scratch wound healing assay, A549 cells incubated with gremlin-1 or transfected with gremlin-1 showed increased migration, which was inhibited in the presence of the GRE1 antibody. Gremlin-1 transfected A549 cells also exhibited increased invasiveness as well as an increased growth rate. These effects were also inhibited by the addition of the GRE1 antibody. In conclusion, this study demonstrates that gremlin-1 directly interacts with cancer cells in a BMP- and VEGFR2-independent manner and can induce cell migration, invasion, and proliferation

Use of carbon-11 acetate and dynamic positron emission tomography to assess regional myocardial oxygen consumption in patients with acute myocardial infarction receiving thrombolysis or coronary angioplasty

Carbon-11 (C-11) acetate has been introduced for the noninvasive measurements of myocardial oxygen consumption. This study was designed to assess regional C-11 acetate clearance in patients with acute myocardial infarction. Thirty-one patients were studied within 8 days of acute myocardial infarction. C-11 acetate washout-rate constants were significantly lower in the infarct territory than in the remote myocardium (p < 0.008). The scintigraphic measurements correlated with heart rate-blood pressure product in the remote as well as infarct areas (0.52 and 0.48, respectively). There was no significant correlation to left ventricular ejection fraction. C-11 washout rates were significantly affected by [beta]receptor therapy as assessed by multiple regression analysis. Thus, C-11 acetate kinetics allow noninvasive characterization of regional myocardial oxygen demand, which may be useful in assessing the extent of myocardial injury and myocardial oxygen demand of remote myocardium.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/30955/1/0000627.pd

Myeloperoxidase and Plasminogen Activator Inhibitor 1 Play a Central Role in Ventricular Remodeling after Myocardial Infarction

Left ventricular (LV) remodeling after myocardial infarction (MI) results in LV dilation, a major cause of congestive heart failure and sudden cardiac death. Ischemic injury and the ensuing inflammatory response participate in LV remodeling, leading to myocardial rupture and LV dilation. Myeloperoxidase (MPO), which accumulates in the infarct zone, is released from neutrophils and monocytes leading to the formation of reactive chlorinating species capable of oxidizing proteins and altering biological function. We studied acute myocardial infarction (AMI) in a chronic coronary artery ligation model in MPO null mice (MPO−/−). MPO−/− demonstrated decreased leukocyte infiltration, significant reduction in LV dilation, and marked preservation of LV function. The mechanism appears to be due to decreased oxidative inactivation of plasminogen activator inhibitor 1 (PAI-1) in the MPO−/−, leading to decreased tissue plasmin activity. MPO and PAI-1 are shown to have a critical role in the LV response immediately after MI, as demonstrated by markedly delayed myocardial rupture in the MPO−/− and accelerated rupture in the PAI-1−/−. These data offer a mechanistic link between inflammation and LV remodeling by demonstrating a heretofore unrecognized role for MPO and PAI-1 in orchestrating the myocardial response to AMI