Tumour development and progression is dependent upon tumour cell interaction with the tissue stroma. Bioengineering the tumour-stroma microenvironment (TME) into 3D biomimetic models is crucial to gain insight into tumour cell development and progression pathways and identify therapeutic targets. Ameloblastoma is a benign but locally aggressive epithelial odontogenic neoplasm that mainly occurs in the jawbone and can cause significant morbidity and sometimes death. The molecular mechanisms for ameloblastoma progression are poorly understood. A spatial model recapitulating the tumour and stroma was engineered to show that without a relevant stromal population, tumour invasion is quantitatively decreased. Where a relevant stroma was engineered in dense collagen populated by gingival fibroblasts, enhanced receptor activator of nuclear factor kappa-B ligand (RANKL) expression was observed and histopathological properties, including ameloblastoma tumour islands, developed and were quantified. Using human osteoblasts (bone stroma) further enhanced the biomimicry of ameloblastoma histopathological phenotypes. This work demonstrates the importance of the two key stromal populations, osteoblasts, and gingival fibroblasts, for accurate 3D biomimetic ameloblastoma modelling.

The BfR MEAL Study aims to provide representative levels of chemical substances in foods consumed by the population in Germany for dietary exposure assessment. Calcium, potassium and phosphorus (Ca, K, P) are essential to obtain physiological functions in humans. Levels were investigated in 356 foods. Foods were purchased representatively, prepared as typically consumed and pooled before analysis. High mean levels were found in milk, dairy products, legumes, nuts, oilseeds and spices as well as chia seeds (Ca, K, P), chewing gum (Ca) and cocoa powder (K). Different levels comparing organically and conventionally produced foods were determined among others in cereal cracker (puffed), olives and tofu. Higher K levels were found in fried compared to boiled potatoes. Similar P levels were mainly found in regionally and seasonally sampled foods. These data provide a substantially improved basis to address dietary exposure assessment of the population in Germany for Ca, K and P.

BACKGROUND: Potential indications for surgery frequently arise in patients awaiting liver transplantation. There is a risk of hepatic decompensation and death triggered by surgical trauma, but this has not been studied in detail in this unique population. We aimed to quantify the impact of surgical interventions in patients awaiting liver transplantation on hepatic function and identify risk factors for decompensation.
METHODS: All surgeries between 2000 and 2018 in patients awaiting liver transplantation in a highvolume German liver transplant center were analyzed retrospectively. Change in liver function measured as indicated by MELD score was assessed and complication rates recorded. The primary endpoint was a composite of an increase in MELD score by > 5 points or death. A logistic regression model was used for multivariate analysis to identify risk factors.
RESULTS: In total, 177 surgical procedures in 148 patients were analyzed. The primary endpoint was reached in 42 cases (23.7%). The overall in-hospital complication rate (including death) was 44.1%. Multivariate analysis identified elevated leukocyte count, perioperative blood transfusion, preoperative presence of ascites, and preoperative circulatory support as independent risk factors for a decline in liver function or death.
CONCLUSIONS: Surgery in patients awaiting liver transplantation carries a relevant risk of hepatic decompensation and death that needs to be considered when deciding whether to perform elective surgery prior to or defer until after liver transplantation.

Cadmium (Cd2+) is considered a human carcinogen as it causes oxidative stress and alters DNA repair responses. However, how Cd2+ is taken up by cells remains unclear. We hypothesized that Cd2+ could be transported into cells via a membrane copper (Cu) transporter, CTR1. CTR1 expression was not affected by Cd2+ exposure at the mRNA or protein level. Stable cell lines overexpressing either hCTR1, in the human liver cell line HepG2, or zCTR1, in the zebrafish liver cell line ZFL, were created to study their responses to Cd2+ insult. It was found that both HepG2 and ZFL cells overexpressing CTR1 had higher Cd2+ uptake and thus became sensitive to Cd2+. In contrast, hCTR1 knockdown in HepG2 cells led to a reduced uptake of Cd2+, making the cells relatively resistant to Cd2+. Localization studies revealed that hCTR1 had a clustered pattern after Cd2+ exposure, possibly in an attempt to reduce both Cd2+ uptake and Cd2+-induced toxicity. These in vitro results indicate that CTR1 can transport Cd2+ into the cell, resulting in Cd2+ toxicity.

Stranded driftwood feedstocks may represent, after pretreatment with steam explosion and enzymatic hydrolysis, a cheap C-source for producing biochemicals and biofuels using oleaginous yeasts. The hydrolysis was optimized using a response surface methodology (RSM). The solid loading (SL) and the dosage of enzyme cocktail (ED) were variated following a central composite design (CCD) aimed at optimizing the conversion of carbohydrates into lipids (YL) by the yeast Solicoccozyma terricola DBVPG 5870. A second-order polynomial equation was computed for describing the effect of ED and SL on YL. The best combination (ED = 3.10%; SL = 22.07%) for releasing the optimal concentration of carbohydrates which gave the highest predicted YL (27.32%) was then validated by a new hydrolysis. The resulting value of YL (25.26%) was close to the theoretical maximum value. Interestingly, fatty acid profile achieved under the optimized conditions was similar to that reported for palm oil.

The preschool environment exerts an important influence on children\'s behaviour, including physical activity (PA). However, information is lacking regarding where and when most of children\'s PA is undertaken. This study aimed to describe PA and sedentary time (SED) during preschool hours and time out-of-care, and on weekdays and weekend days, and to investigate differences in PA patterns according to sex, age, and MVPA levels. From September 2015 to June 2016, we measured PA levels of 1109 children (age range, 2.7-6.5 years; mean age 4.7 years; boys, 52%) using ActiGraph GT3X+ accelerometers for up to 14 consecutive days. We applied a linear mixed model to analyse associations and interactions between total PA (counts per minute [cpm]), light PA (LPA), moderate-to-vigorous PA (MVPA), SED, sex, age, and overall MVPA regardless of setting, during preschool hours versus time out-of-care, and on weekdays versus weekend days. Children undertook more PA and less SED on weekdays compared to weekend days (p < 0.01). For boys, MVPA levels were higher during preschool hours than during time out-of-care (p < 0.05). Differences in total PA and MVPA between preschool hours versus time out-of-care, and between weekdays and weekend days, were greater in boys, older children, and highly active children than in girls, younger children, and children with lower overall MVPA levels (p < 0.01). The preschool arena is important for children\'s PA. Concerning MVPA, this study showed that boys, older children, and highly active children benefit more from this environment compared to girls, younger preschoolers, and children with lower MVPA levels.

BACKGROUND: Due to its availability, atenolol is the primary beta-blocker used in Australia for children with long QT syndrome. There is limited data on long-term follow-up of its use.
METHODS: A single-tertiary-center, retrospective, observational study investigating all children and adolescents who had genetically proven long QT syndrome type 1 (LQT1) and type 2 (LQT2) was conducted. Their pretreatment exercise tests were evaluated for QTc intervals into the recovery phase of exercise.
RESULTS: Eighty six patients were identified (LQT1, 67, and LQT2, 19) from 2004 to 2014. The majority (86%) of patients were initially referred for family screening. Atenolol was administered at a mean dose of 1.58 ± 0.51 mg/kg/day. During the median follow-up period of 4.29 years, only one proband developed ventricular arrhythmia whilst taking atenolol, No patient had cardiac arrest or aborted cardiac arrest. With respect to side effects of atenolol, only two patients had intolerable side effects necessitating changes of medication. Evaluation of exercise tests (pretreatment) demonstrated that corrected QT (QTc) intervals at 2-3 min into the recovery phase of exercise were significantly prolonged for LQT1 patients. LQT1 patients with transmembrane mutation had longer QTc intervals than their C-terminus mutation counterparts, reaching statistical significance at 3 min into the recovery phase of exercise.
CONCLUSIONS: Atenolol is an effective treatment for genetically proven LQT1 and LQT2 children and adolescents, with good tolerability. In LQT1 patients, QTc intervals at 2-3 min into the recovery phase of exercise were significantly prolonged, particularly in patients with transmembrane mutations.

The demands for applicable tissue-engineered scaffolds that can be used to repair load-bearing segmental bone defects (SBDs) is vital and in increasing demand. In this study, seven different combinations of 3 dimensional (3D) novel nanocomposite porous structured scaffolds were fabricated to rebuild SBDs using an extraordinary blend of cockle shells (CaCo3) nanoparticles (CCN), gelatin, dextran and dextrin to structure an ideal bone scaffold with adequate degradation rate using the Freeze Drying Method (FDM) and labeled as 5211, 5400, 6211, 6300, 7101, 7200 and 8100. The micron sized cockle shells powder obtained (75 µm) was made into nanoparticles using mechano-chemical, top-down method of nanoparticles synthesis with the presence of the surfactant BS-12 (dodecyl dimethyl bataine). The phase purity and crystallographic structures, the chemical functionality and the thermal characterization of the scaffolds\' powder were recognized using X-Ray Diffractometer (XRD), Fourier transform infrared (FTIR) spectrophotometer and Differential Scanning Calorimetry (DSC) respectively. Characterizations of the scaffolds were assessed by Scanning Electron Microscopy (SEM), Degradation Manner, Water Absorption Test, Swelling Test, Mechanical Test and Porosity Test. Top-down method produced cockle shell nanoparticles having averagely range 37.8±3-55.2±9 nm in size, which were determined using Transmission Electron Microscope (TEM). A mainly aragonite form of calcium carbonate was identified in both XRD and FTIR for all scaffolds, while the melting (Tm) and transition (Tg) temperatures were identified using DSC with the range of Tm 62.4-75.5 °C and of Tg 230.6-232.5 °C. The newly prepared scaffolds were with the following characteristics: (i) good biocompatibility and biodegradability, (ii) appropriate surface chemistry and (iii) highly porous, with interconnected pore network. Engineering analyses showed that scaffold 5211 possessed 3D interconnected homogenous porous structure with a porosity of about 49%, pore sizes ranging from 8.97 to 337 µm, mechanical strength 20.3 MPa, Young\'s Modulus 271±63 MPa and enzymatic degradation rate 22.7 within 14 days.

Bioconversion of hemicellulosic hydrolysate into ethanol plays a pivotal role in the overall success of biorefineries. For the efficient fermentative conversion of hemicellulosic hydrolysates into ethanol, the use of immobilized cells system could provide the enhanced ethanol productivities with significant time savings. Here, we investigated the effect of 2 important factors (e.g., cell concentration and stirring) on ethanol production from sugarcane bagasse hydrolysate using the yeast Scheffersomyces stipitis immobilized in calcium alginate matrix. A 2(2) full factorial design of experiment was performed considering the process variables- immobilized cell concentration (3.0, 6.5 and 10.0 g/L) and stirring (100, 200 and 300 rpm). Statistical analysis showed that stirring has the major influence on ethanol production. Maximum ethanol production (8.90 g/l) with ethanol yield (Yp/s) of 0.33 g/g and ethanol productivity (Qp) of 0.185 g/l/h was obtained under the optimized process conditions (10.0 g/L of cells and 100 rpm).