The ability of Myc to promote cellular transformation is well established; however, a better understanding of the mechanisms through which Myc mediates tumorigenesis is essential for the development of therapeutic approaches to target this potent oncoprotein. Structure-function studies in rodent fibroblast cells have provided the basis for much of our current understanding of these mechanisms. To build on these approaches, we have characterized three novel human cell line models of Myc-dependent transformation: MCF10A, SH-EP Tet21/N-Myc, and LF1/TERT/LT/ST cells. We have also evaluated Myc family proteins (c-Myc and L-Myc), a naturally occurring isoform of Myc (MycS), and a set of N-terminal domain mutants (DMBII, W135E, T58A) for their ability to promote anchorage-independent growth in these models. Taken together, these results provide the field with three new human cell-based models to study Myc activity, highlight the importance of cellular context, and challenge the paradigm that the ability of Myc to promote tumorigenesis is exclusively MBII-dependent.
This Case Study gives an account of the factors that led up to the joint commissioning unit (JCU) within the health and social services scene in Shropshire; analyses the concept of strategic joint commissioning; and describes the role of the JCU and how it works.
Background: Endoscopic and open carpal tunnel releases (ECTR and OCTR) are safe and effective operations. We compared the approaches in terms of postoperative opioid refills and occupational therapy (OT) referrals. Methods: We conducted a retrospective study of patients with carpal tunnel syndrome (CTS) treated with ECTR or OCTR. Patients with isolated idiopathic CTS were included; patients undergoing simultaneous bilateral carpal tunnel release (CTR), revision CTR, and additional procedures at time of CTR were excluded. Outcomes included number of patients requiring an opioid refill and/or an OT referral within 6 months of surgery. Results: A total of 1125 patients met inclusion criteria. Endoscopic release was performed in 634 (56%) cases and open release in 491 (44%). Unadjusted analysis revealed no difference in number of patients requiring refills (6.0% vs 7.1%, P = .44), mean number of refills among those requiring one (1.29 vs 1.23, P = .69), total oral morphine equivalents (45.1 vs 44.7, P = .84), number of patients calling regarding pain (12.8% vs 14.7%, P = .36), OT referrals (12.1% vs 11.4%, P = .71), or average number of OT visits (4.5 vs 4.2, P = .74) for endoscopic and open techniques, respectively. Adjusted analysis revealed lower age, lower body mass index, and history of muscle relaxant as predictors of opioid refills, and in contrast to the unadjusted analysis, operating surgeon and surgical technique were predictors of referral to OT. Conclusion: Endoscopic CTR and OCTR did not differ in terms of unadjusted postoperative patient calls for pain, number of opioid refills, or OT referrals. After correcting for individual surgeon practice, endoscopic was associated with decreased odds of requiring postoperative OT.
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