Secondary Repair of Jersey Finger: A Novel Method of Tendon Length Estimation via Measurement of Adjacent Landmarks.

Jersey finger describes the rupture of the flexor digitorum profundus (FDP) tendon at its insertion into the distal phalanx. In the absence of an evidence-based approach to tensioning during secondary repair, we aimed to devise a novel method to determine the required tendon length pre/intraoperatively. We measured anatomical landmarks, associated with the FDP tendon, on dissected cadavers, to assess whether these can be used to estimate tendon segment lengths. Eight cadaveric hands were dissected. Three measurements from the distal lumbrical origin to (1) FDP insertion, (2) the distal end of A1 (Annular 1 pulley), and (3) the proximal end of A1 were recorded for digits II-V. Relative ratios for measurement 1 were consistent for all digits, compared to digit III. Linear regression analysis confirmed a strong correlation for measurement 1 between digit II (R2 =0.97) and digit IV(R2 =0.97) compared to digit III across all specimens. Digit III distal lumbrical origin to FDP insertion measurements could facilitate the estimation of the required graft length for digit II or IV during secondary repair. This is a level IV study, providing proof of concept for a novel method of tendon tensioning.

A qualitative study of the incentives and barriers that influence preferences for rural placements during surgical training in Australia.

BACKGROUND: Rural exposure of long durations during clinical training is positively associated with rural career uptake and is a central strategy to addressing the geographical maldistribution of Australia's surgical workforce. However, the incentives and barriers to trainees undergoing surgical training preferencing repeated rural placements in Australia are not well understood. This qualitative study explores the incentives and barriers that influence preference for rural placements during surgical training in Australia. METHODS: This qualitative study employed online semi-structured in-depth interviews. Participants were recruited using an online survey, and interviews were conducted between October 2020 and November 2020. Transcripts were transcribed and de-identified, and thematically analysed. RESULTS: Twenty-nine semi-structured interviews were conducted with trainees and 12 Fellows. Twenty-five participants identified as male, and four identified as female. Four main incentives identified were: (1) broad scope of learning opportunities, (2) quality of supervision, (3) positive work environment and (4) lifestyle. Seven barriers identified were: (1) inadequate preparation for placement, (2) limited case mix to support learning outcomes, (3) lack of formally structured learning opportunities, (4) workload and safe hours concerns, (5) lack of peer support, (6) childcare and educational needs and (7) partner career development. CONCLUSION: The strategy of encouraging trainees to undertake rural placements to address the maldistribution of the surgical workforce should include initiatives that support learning outcomes across their training levels. In addition, improving trainees' ability to prepare adequately for placements may also improve the number and duration of rural placements trainees undertake during their training.

PTTG and PBF Functionally Interact with p53 and Predict Overall Survival in Head and Neck Cancer.

Head and neck squamous cell carcinoma (HNSCC) is the 6th most common cancer worldwide and poses a significant health burden due to its rising incidence. Although the proto-oncogene pituitary tumor-transforming gene 1 (PTTG) predicts poor patient outcome, its mechanisms of action are incompletely understood. We show here that the protein PBF modulates PTTG function, is overexpressed in HNSCC tumors, and correlates with significantly reduced survival. Lentiviral shRNA attenuation of PTTG or PBF expression in HNSCC cells with either wild-type or mutant p53, and with and without HPV infection, led to dysregulated expression of p53 target genes involved in DNA repair and apoptosis. Mechanistically, PTTG and PBF affected each other's interaction with p53 and cooperated to reduce p53 protein stability in HNSCC cells independently of HPV. Depletion of either PTTG or PBF significantly repressed cellular migration and invasion and impaired colony formation in HNSCC cells, implicating both proto-oncogenes in basic mechanisms of tumorigenesis. Patients with HNSCC with high tumoral PBF and PTTG had the poorest overall survival, which reflects a marked impairment of p53-dependent signaling.Significance: These findings reveal a complex and novel interrelationship between the expression and function of PTTG, PBF, and p53 in human HNSCC that significantly influences patient outcome. Cancer Res; 78(20); 5863-76. ©2018 AACR.

Angiogenic potential of endothelial progenitor cells and embryonic stem cells.

BACKGROUND: Endothelial progenitor cells (EPCs) are implicated in a range of pathological conditions, suggesting a natural therapeutic role for EPCs in angiogenesis. However, current angiogenic therapies involving EPC transplantation are inefficient due to rejection of donor EPCs. One solution is to derive an expanded population of EPCs from stem cells in vitro, to be re-introduced as a therapeutic transplant. To demonstrate the therapeutic potential of EPCs we performed in vitro transplantation of EPCs into endothelial cell (EC) tubules using a gel-based tubule formation assay. We also described the production of highly angiogenic EPC-comparable cells from pluripotent embryonic stem cells (ESCs) by direct differentiation using EC-conditioned medium (ECCM). RESULTS: The effect on tubule complexity and longevity varied with transplantation quantity: significant effects were observed when tubules were transplanted with a quantity of EPCs equivalent to 50% of the number of ECs originally seeded on to the assay gel but not with 10% EPC transplantation. Gene expression of the endothelial markers VEGFR2, VE-cadherin and CD31, determined by qPCR, also changed dynamically during transplantation. ECCM-treated ESC-derived progenitor cells exhibited angiogenic potential, demonstrated by in vitro tubule formation, and endothelial-specific gene expression equivalent to natural EPCs. CONCLUSIONS: We concluded the effect of EPCs is cumulative and beneficial, relying on upregulation of the angiogenic activity of transplanted cells combined with an increase in proliferative cell number to produce significant effects upon transplantation. Furthermore, EPCs derived from ESCs may be developed for use as a rapidly-expandable alternative for angiogenic transplantation therapy.

A major predisposition locus for severe obesity, at 4p15-p14.

Although the predisposition to morbid obesity is heritable, the identities of the disease-causing genes are largely unknown. Therefore, we have conducted a genomewide search with 628 markers, using multigenerational Utah pedigrees to identify genes involved in predisposition to obesity. In the genomewide search, we identified a highly significant linkage to high body-mass index in female patients, at D4S2632, with a multipoint heterogeneity LOD (HLOD) score of 6.1 and a nonparametric linkage (NPL) score of 5.3. To further delineate the linkage, we increased both the marker density around D4S2632 and the size of our pedigree data set. As a result, the linkage evidence increased to a multipoint HLOD score of 9.2 (at D4S3350) and an NPL score of 11.3. Evidence from almost half of the families in this analysis support this linkage, and therefore the gene in this region might account for a significant percentage of the genetic predisposition to severe obesity in females. However, further studies are necessary to clarify the effect that this gene has in males and in the general population.