Comparison of Metzenbaum scissors and Y-shaped fasciotome for deep metatarsal fasciotomy for the treatment of proximal suspensory ligament desmopathy in horses.

OBJECTIVE: To quantitate the iatrogenic injury associated with deep plantar metatarsal fasciotomy performed with Metzenbaum scissors compared with a Y-shaped fasciotome. STUDY DESIGN: Experimental ex vivo surgical study. STUDY POPULATION: Cadaveric hind limbs (n = 20) from 10 sound thoroughbred racehorses. METHODS: A plantar metatarsal fasciotomy was performed, extending from the proximal extent of the deep metatarsal fascia, distally. Hind limbs were randomly assigned to 2 groups, undergoing fasciotomy with straight Metzenbaum scissors (n = 10) or a Y-shaped fasciotome (n = 10). Magnetic resonance imaging was performed before and after surgery to identify the maximal depth of any iatrogenic trauma. Gross examination of the surgical site included measuring the length of the incision in the deep metatarsal fascia and localizing iatrogenic trauma sustained by the plantar aspect of the proximal suspensory ligament (PSL) during the procedure. RESULTS: Iatrogenic injury to the PSL was identified in 6 of 10 and 9 of 10 specimens prepared with the fasciotome and Metzenbaum scissors, respectively (P = .03), and was most commonly located in the distal third of the fascial incision. Differences between the length of incision (P = .02) and the maximal depth of signal (P = .03) for incisions created with Metzenbaum scissors or a fasciotome were identified. CONCLUSION: The use of a fasciotome resulted in longer fascial incisions and less severe iatrogenic trauma to the PSL compared with using Metzenbaum scissors. CLINICAL SIGNIFICANCE: A Y-shaped fasciotome may be the preferred surgical instrument for successful desmopathy of the PSL fasciotomy because a greater release of compartmental pressure is possible through a longer incision with minimal iatrogenic trauma to the underlying PSL.

Perceptions of Infertility and Reproductive Concerns in Adolescent and Young Adult Female Cancer Survivors.

This cross-sectional survey study explores the fertility perceptions of adolescent and young adult female cancer survivors (n = 111) and relationships to fertility counseling and reproductive distress. Satisfaction with post-treatment fertility counseling (ß = -0.20, p = 0.04), perceived consequences of cancer-related fertility changes (ß = 0.26, p = 0.03), and understanding of one's reproductive health (ß = -0.22, p = 0.03) correlated with reproductive distress, controlling for covariates (F(10, 88) = 3.50, p < 0.001). Findings suggest that post-treatment counseling may be important to addressing survivors' perceptions of fertility and reproductive potential, which influences levels of distress and to create a greater sense of control on their road to parenthood.

Cancer and Fertility: Exploring Uncertainty Management Strategies of Young Adult Female Survivors.

This study describes young adult female (YA-F) cancer survivors' uncertainty management strategies related to fertility/family building. Cross-sectional data were analyzed (n = 98). Participants reported higher rates of seeking information to reduce fertility-related uncertainty (M = 5.48, ±1.03), than avoiding information (M = 4.77, ±1.29). Controlling for relevant covariates (i.e., reproductive distress, household income, and health literacy), greater avoidance was related to higher reproductive distress (ß = 0.293, p = 0.011) and lower household income (ß = -0.281, p = 0.047). Evidence suggests that some survivors may avoid fertility-related information to manage uncertainty and distress, which may impact family-building success. Fertility avoidance may be an important target of intervention.

The EBV-Encoded Oncoprotein, LMP1, Recruits and Transforms Fibroblasts via an ERK-MAPK-Dependent Mechanism.

Latent membrane protein 1 (LMP1), the major oncoprotein encoded by Epstein-Barr virus (EBV), is expressed at widely variable levels in undifferentiated nasopharyngeal carcinoma (NPC) biopsies, fueling intense debate in the field as to the importance of this oncogenic protein in disease pathogenesis. LMP1-positive NPCs are reportedly more aggressive, and in a similar vein, the presence of cancer-associated fibroblasts (CAFs) surrounding "nests" of tumour cells in NPC serve as indicators of poor prognosis. However, there is currently no evidence linking LMP1 expression and the presence of CAFs in NPC. In this study, we demonstrate the ability of LMP1 to recruit fibroblasts in vitro in an ERK-MAPK-dependent mechanism, along with enhanced viability, invasiveness and transformation to a myofibroblast-like phenotype. Taken together, these findings support a putative role for LMP1 in recruiting CAFs to the tumour microenvironment in NPC, ultimately contributing to metastatic disease.

The EBV-Encoded Oncoprotein, LMP1, Induces an Epithelial-to-Mesenchymal Transition (EMT) via Its CTAR1 Domain through Integrin-Mediated ERK-MAPK Signalling.

The Epstein⁻Barr virus (EBV)-encoded latent membrane protein 1 (LMP1) oncogene can induce profound effects on epithelial growth and differentiation including many of the features of the epithelial-to-mesenchymal transition (EMT). To better characterise these effects, we used the well-defined Madin Darby Canine Kidney (MDCK) epithelial cell model and found that LMP1 expression in these cells induces EMT as defined by characteristic morphological changes accompanied by loss of E-cadherin, desmosomal cadherin and tight junction protein expression. The induction of the EMT phenotype required a functional CTAR1 domain of LMP1 and studies using pharmacological inhibitors revealed contributions from signalling pathways commonly induced by integrin⁻ligand interactions: extracellular signal-regulated kinases/mitogen-activated protein kinases (ERK-MAPK), PI3-Kinase and tyrosine kinases, but not transforming growth factor beta (TGFβ). More detailed analysis implicated the CTAR1-mediated induction of Slug and Twist in LMP1-induced EMT. A key role for β1 integrin signalling in LMP1-mediated ERK-MAPK and focal adhesion kianse (FAK) phosphorylation was observed, and β1 integrin activation was found to enhance LMP1-induced cell viability and survival. These findings support an important role for LMP1 in disease pathogenesis through transcriptional reprogramming that enhances tumour cell survival and leads to a more invasive, metastatic phenotype.

The Epstein-Barr virus encoded LMP1 oncoprotein modulates cell adhesion via regulation of activin A/TGFß and ß1 integrin signalling.

Approximately 20% of global cancer incidence is causally linked to an infectious agent. Epstein-Barr virus (EBV) accounts for around 1% of all virus-associated cancers and is associated with nasopharyngeal carcinoma (NPC). Latent membrane protein 1 (LMP1), the major oncoprotein encoded by EBV, behaves as a constitutively active tumour necrosis factor (TNF) receptor activating a variety of signalling pathways, including the three classic MAPKs (ERK-MAPK, p38 MAPK and JNK/SAPK). The present study identifies novel signalling properties for this integral membrane protein via the induction and secretion of activin A and TGFß1, which are both required for LMP1's ability to induce the expression of the extracellular matrix protein, fibronectin. However, it is evident that LMP1 is unable to activate the classic Smad-dependent TGFß signalling pathway, but rather elicits its effects through the non-Smad arm of TGFß signalling. In addition, there is a requirement for JNK/SAPK signalling in LMP1-mediated fibronectin induction. LMP1 also induces the expression and activation of the major fibronectin receptor, α5ß1 integrin, an effect that is accompanied by increased focal adhesion formation and turnover. Taken together, these findings support the putative role for LMP1 in the pathogenesis of NPC by contributing to the metastatic potential of epithelial cells.