Neo-Anal Sphincter Fabrication in the Rat

Undergraduate Research Opportunity Program (UROP)http://deepblue.lib.umich.edu/bitstream/2027.42/116119/1/Neo_Anal_SphincterFabrication_Rats.pd

Non-invasive muscle contraction assay to study rodent models of sarcopenia

<p>Abstract</p> <p>Background</p> <p>Age-related sarcopenia is a disease state of loss of muscle mass and strength that affects physical function and mobility leading to falls, fractures, and disability. The need for therapies to treat age-related sarcopenia has attracted intensive preclinical research. To facilitate the discovery of these therapies, we have developed a non-invasive rat muscle functional assay system to efficiently measure muscle force and evaluate the efficacy of drug candidates.</p> <p>Methods</p> <p>The lower leg muscles of anesthetized rats are artificially stimulated with surface electrodes on the knee holders and the heel support, causing the lower leg muscles to push isometric pedals that are attached to force transducers. We developed a stimulation protocol to perform a fatigability test that reveals functional muscle parameters like maximal force, the rate of fatigue, fatigue-resistant force, as well as a fatigable muscle force index. The system is evaluated in a rat aging model and a rat glucocorticoid-induced muscle loss model</p> <p>Results</p> <p>The aged rats were generally weaker than adult rats and showed a greater reduction in their fatigable force when compared to their fatigue-resistant force. Glucocorticoid treated rats mostly lost fatigable force and fatigued at a higher rate, indicating reduced force from glycolytic fibers with reduced energy reserves.</p> <p>Conclusions</p> <p>The involuntary contraction assay is a reliable system to assess muscle function in rodents and can be applied in preclinical research, including age-related sarcopenia and other myopathy.</p

"Accuracy of Predicted Resection Weights in Breast Reduction Surgery"

Background: Many insurance carriers continue to deny coverage for reduction mammaplasty unless a minimum amount of resected breast tissue per breast is achieved during surgery. This study investigates the accuracy of preoperative prediction that a minimum weight of 500 g can be resected and evaluates potential risk factors for not meeting this insurance requirement. Methods: A retrospective review was performed on 445 patients with bilateral symptomatic macromastia who sought consultation for breast reduction surgery from 2007 to 2012. Women were included for analysis if they had documented predicted resection weights and underwent small-to-moderate breast reduction (< 1,000 g per side; n = 323). Relevant demographic information, mean predicted resection weight, and the mean actual resection weight were collected for analysis. Results: Surgeon prediction of resection weight being over 500 g had a positive predictive value of 73%. In 61 patients (19%), the predicted weights were ≥ 500 g, but the actual weights were < 500 g. Thirty percentage of these 61 patients did not meet either Schnur or minimum weight requirements. Women with a body mass index < 30 were at significantly increased odds (odds ratio, 3.76; 95% confidence interval, 1.89-7.48; P = 0.002) of not meeting the minimum weight requirement at surgery compared with patients with a body mass index ≥ 30. Conclusions: The common insurance criterion of removing ≥ 500 g per breast during breast reduction surgery are not met in a distinct cohort of women who are clinically appropriate candidates. This risk is particularly increased in nonobese women possibly due to proportionately smaller breast mass compared with obese women.http://deepblue.lib.umich.edu/bitstream/2027.42/175850/2/Accuracy of Predicted Resection Weights in Breast Reduction Surgery.pdfPublished versio

NGF-TrkA signaling dictates neural ingrowth and aberrant osteochondral differentiation after soft tissue trauma

Pain is a central feature of soft tissue trauma, which under certain contexts, results in aberrant osteochondral differentiation of tissue-specific stem cells. Here, the role of sensory nerve fibers in this abnormal cell fate decision is investigated using a severe extremity injury model in mice. Soft tissue trauma results in NGF (Nerve growth factor) expression, particularly within perivascular cell types. Consequently, NGF-responsive axonal invasion occurs which precedes osteocartilaginous differentiation. Surgical denervation impedes axonal ingrowth, with significant delays in cartilage and bone formation. Likewise, either deletion of Ngf or two complementary methods to inhibit its receptor TrkA (Tropomyosin receptor kinase A) lead to similar delays in axonal invasion and osteochondral differentiation. Mechanistically, single-cell sequencing suggests a shift from TGFβ to FGF signaling activation among pre-chondrogenic cells after denervation. Finally, analysis of human pathologic specimens and databases confirms the relevance of NGF-TrkA signaling in human disease. In sum, NGF-mediated TrkA-expressing axonal ingrowth drives abnormal osteochondral differentiation after soft tissue trauma. NGF-TrkA signaling inhibition may have dual therapeutic use in soft tissue trauma, both as an analgesic and negative regulator of aberrant stem cell differentiation