MUG Mel3 Cell Lines Reflect Heterogeneity in Melanoma and Represent a Robust Model for Melanoma in Pregnancy.

Melanomas are aggressive tumors with a high metastatic potential and an increasing incidence rate. They are known for their heterogeneity and propensity to easily develop therapy-resistance. Nowadays they are one of the most common cancers diagnosed during pregnancy. Due to the difficulty in balancing maternal needs and foetal safety, melanoma is challenging to treat. The aim of this study was to provide a potential model system for the study of melanoma in pregnancy and to illustrate melanoma heterogeneity. For this purpose, a pigmented and a non-pigmented section of a lymph node metastasis from a pregnant patient were cultured under different conditions and characterized in detail. All four culture conditions exhibited different phenotypic, genotypic as well as tumorigenic properties, and resulted in four newly established melanoma cell lines. To address treatment issues, especially in pregnant patients, the effect of synthetic human lactoferricin-derived peptides was tested successfully. These new BRAF-mutated MUG Mel3 cell lines represent a valuable model in melanoma heterogeneity and melanoma pregnancy research. Furthermore, treatment with anti-tumor peptides offers an alternative to conventionally used therapeutic options-especially during pregnancy.

CPR with restricted patient access using alternative rescuer positions: a randomised cross-over manikin study simulating the CPR scenario after avalanche burial.

BACKGROUND: The aim of this manikin study was to evaluate the quality of cardiopulmonary resuscitation (CPR) with restricted patient access during simulated avalanche rescue using over-the-head and straddle position as compared to standard position. METHODS: In this prospective, randomised cross-over study, 25 medical students (64% male, mean age 24) performed single-rescuer CPR with restricted patient access in over-the-head and straddle position using mouth-to-mouth ventilation or pocket mask ventilation. Chest compression depth, rate, hand position, recoil, compression/decompression ratio, hands-off times, tidal volume of ventilation and gastric insufflation were compared to CPR with unrestricted patient access in standard position. RESULTS: Only 28% of all tidal volumes conformed to the guidelines (400-800 ml), 59% were below 400 ml and 13% were above 800 ml. There was no significant difference in ventilation parameters when comparing standard to atypical rescuer positions. Participants performed sufficient chest compressions depth in 98.1%, a minimum rate in 94.7%, correct compression recoil in 43.8% and correct hand position in 97.3% with no difference between standard and atypical rescuer positions. In 36.9% hands-off times were longer than 9 s. CONCLUSIONS: Efficacy of CPR from an atypical rescuer position with restricted patient access is comparable to CPR in standard rescuer position. Our data suggest to start basic life-support before complete extrication in order to reduce the duration of untreated cardiac arrest in avalanche rescue. Ventilation quality provided by lay rescuers may be a limiting factor in resuscitation situations where rescue ventilation is considered essential.

Electrospun PCL/PLA Scaffolds Are More Suitable Carriers of Placental Mesenchymal Stromal Cells Than Collagen/Elastin Scaffolds and Prevent Wound Contraction in a Mouse Model of Wound Healing.

Mesenchymal stem/stromal cells (MSCs) exert beneficial effects during wound healing, and cell-seeded scaffolds are a promising method of application. Here, we compared the suitability of a clinically used collagen/elastin scaffold (Matriderm) with an electrospun Poly(ε-caprolactone)/poly(l-lactide) (PCL/PLA) scaffold as carriers for human amnion-derived MSCs (hAMSCs). We created an epidermal-like PCL/PLA scaffold and evaluated its microstructural, mechanical, and functional properties. Sequential spinning of different PCL/PLA concentrations resulted in a wide-meshed layer designed for cell-seeding and a dense-meshed layer for apical protection. The Matriderm and PCL/PLA scaffolds then were seeded with hAMSCs, with or without Matrigel coating. The quantity and quality of the adherent cells were evaluated in vitro. The results showed that hAMSCs adhered to and infiltrated both scaffold types but on day 3, more cells were observed on PCL/PLA than on Matriderm. Apoptosis and proliferation rates were similar for all carriers except the coated Matriderm, where apoptotic cells were significantly enhanced. On day 8, the number of cells decreased on all carrier types except the coated Matriderm, which had consistently low cell numbers. Uncoated Matriderm had the highest percentage of proliferative cells and lowest apoptosis rate of all carrier types. Each carrier also was topically applied to skin wound sites in a mouse model and analyzed in vivo over 14 days via optical imaging and histological methods, which showed detectable hAMSCs on all carrier types on day 8. On day 14, all wounds exhibited newly formed epidermis, and all carriers were well-integrated into the underlying dermis and showing signs of degradation. However, only wounds treated with uncoated PCL/PLA maintained a round appearance with minimal contraction. Overall, the results support a 3-day in vitro culture of scaffolds with hAMSCs before wound application. The PCL/PLA scaffold showed higher cell adherence than Matriderm, and the effect of the Matrigel coating was negligible, as all carrier types maintained sufficient numbers of transplanted cells in the wound area. The anti-contractive effects of the PCL/PLA scaffold offer potential new therapeutic approaches to wound care.

Literacy Training of Kindergarten Children With Pencil, Keyboard or Tablet Stylus: The Influence of the Writing Tool on Reading and Writing Performance at the Letter and Word Level.

During the last years, digital writing devices are increasingly replacing handwriting with pencil and paper. As reading and writing skills are central for education, it is important to know, which writing tool is optimal for initial literacy education. The present training study was therefore set up to test the influence of the writing tool on the acquisition of literacy skills at the letter and word level with various tests in a large sample of kindergarten children (n = 147). Using closely matched letter learning games, children were trained with 16 letters by handwriting with a pencil on a sheet of paper, by writing with a stylus on a tablet computer, or by typing letters using a virtual keyboard on a tablet across 7 weeks. Training using a stylus on a touchscreen is an interesting comparison condition for traditional handwriting, because the slippery surface of a touchscreen has lower friction than paper and thus increases difficulty of motor control. Before training, immediately after training and four to five weeks after training, we assessed reading and writing performance using standardized tests. We also assessed visuo-spatial skills before and after training, in order to test, whether the different training regimens affected cognitive domains other than written language. Children of the pencil group showed superior performance in letter recognition and improved visuo-spatial skills compared with keyboard training. The performance of the stylus group did not differ significantly neither from the keyboard nor from the pencil group. Keyboard training, however, resulted in superior performance in word writing and reading compared with handwriting training with a stylus on the tablet, but not compared with the pencil group. Our results suggest that handwriting with pencil fosters acquisition of letter knowledge and improves visuo-spatial skills compared with keyboarding. At least given the current technological state, writing with a stylus on a touchscreen seems to be the least favorable writing tool, possibly because of increased demands on motor control. Future training studies covering a more extended observation period over years are needed to allow conclusions about long-term effects of writing tools on literacy acquisition as well as on general cognitive development.