We report on whole-exome sequencing (WES) of 213 melanomas. Our analysis established NF1, encoding a negative regulator of RAS, as the third most frequently mutated gene in melanoma, after BRAF and NRAS. Inactivating NF1 mutations were present in 46% of melanomas expressing wild-type BRAF and RAS, occurred in older patients and showed a distinct pattern of co-mutation with other RASopathy genes, particularly RASA2. Functional studies showed that NF1 suppression led to increased RAS activation in most, but not all, melanoma cases. In addition, loss of NF1 did not predict sensitivity to MEK or ERK inhibitors. The rebound pathway, as seen by the induction of phosphorylated MEK, occurred in cells both sensitive and resistant to the studied drugs. We conclude that NF1 is a key tumor suppressor lost in melanomas, and that concurrent RASopathy gene mutations may enhance its role in melanomagenesis.

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Stem cells can increase the rate of bone healing by differentiating into certain tissues. It is predicted that adipose tissue-derived SVF rich with mesenchymal stem cells can increase bone healing in facial bone defects and this application could replace the use of bone grafts and flaps in clinical practice. As a result, it is concluded that adipose tissue-derived stem cells can potentiate osteogenesis and reduce the possibility of developing necrosis on the bone ends.

Optimal vascularisation of the graft site is significant for improving the outcome of fat grafting. Adipose tissue, specifically the stromal vascular fraction (SVF), is known to regulate its own vascular network. In order to assess the production of angiogenetic growth factors, this study investigated the content of insulin growth factor (IGF), vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), platelet-derived growth factor (PDGF), leptin, and metallothioneine-9 (MMP-9) in the SVF after incubation in differentiation or proliferation media. The SVF was isolated from human subcutaneous adipose tissue. Cells were either cultured in proliferation medium (PM) or in differentiation medium (DM). The samples were analysed for the respective factors using ELISA after 3 and 6 days. The GF levels showed a distinctive characteristic over time depending on the culture medium. IGF, PDGF, and MMP-9 levels decreased with PM and increased with DM. VEGF levels were increased in both media. Leptin showed a decrease in both media. The differentiation medium was associated with high inter-individual distribution in growth factor production except for PDGF and Leptin. In conclusion, incubation with differentiation medium produces a more reliable increase of selected growth factors than incubation with proliferation medium. Enrichment of fat grafts with growth factor-activated autologous SVF samples could help to enable better ingrowth of the transplanted tissue and a more stable outcome. The scattering of the results could explain the inter-individual differences regarding the outcome.

Objective: This study aimed to investigate whether there was an increase in the number of postoperative complications in patients undergoing reduction mammoplasty depending on the technique used (i.e., pedicle type, skin incision pattern), existence of concomitant diseases, and presence of other risk factors.Materials and Methods: A total of 186 patients who underwent breast reduction between 2013 and 2018 (bilateral, n = 170; unilateral, n = 16) were included in the study. A retrospective review of the data of patients who underwent reduction mammoplasty, which was performed by the same surgical team in a single institution over a 6-year period, was carried out. Superomedial, superior, and inferior pedicles were used in 99, 55, and 32 patients, respectively. The median follow-up period was 4 years. Results:The median patient age was 45 (range: 16-75) years. The median total reduction weight was 2,194 (range: 80-4,800) grams. The median distance between the sternal notch and nipple was 31 cm (range: 24-45 cm) for the right breast and 30 cm (range: 22-45 cm) for the left breast. The overall complication rate was 6.9%. The complication rates in patients with and without any concomitant diseases were 10.2% and 4.6%, respectively. The overall complication rate was significantly higher in patients with smoking habit, accessory breasts, progesterone use, cerebrovascular disease, morbid obesity (Body Mass Index ≥40 kg/m 2 ), and thalassemia. Conclusion:Our analysis shows that the presence of concomitant diseases increases the risk for postoperative complications in patients who underwent reduction mammoplasty. Our findings do not suggest that any of the techniques have significant superiority to each other in terms of pedicle safety and overall complication rate.