Many drug delivery systems rely on degradation or dissolution of the carrier material to regulate release. In cases where mechanical support is required during regeneration, this necessitates composite systems in which the mechanics of the implant are decoupled from the drug release profile. To address this need, we developed a system in which microspheres (MS) were sequestered in a defined location between two nanofibrous layers. This bilayer delivery system (BiLDS) enables simultaneous structural support and decoupled release profiles. To test this new system, PLGA (poly-lactide-co-glycolic acid) microspheres were prepared using a water-in-oil-in-water (w/o/w) emulsion technique and incorporated Alexa Fluor-tagged bovine serum albumin (BSA) and basic fibroblast growth factor (bFGF). These MS were secured in a defined pocket between two polycaprolactone (PCL) nanofibrous scaffolds, where the layered scaffolds provide a template for new tissue formation while enabling independent and local release from the co-delivered MS. Scanning electron microscopy (SEM) images showed that the assembled BiLDS could localize and retain MS in the central pocket that was surrounded by a continuous seal formed along the margin. Cell viability and proliferation assays showed enhanced cell activity when exposed to BiLDS containing Alexa Fluor-BSA/bFGF-loaded MS, both in vitro and in vivo. MS delivered via the BiLDS system persisted in a localized area after subcutaneous implantation for at least 4 weeks, and bFGF release increased colonization of the implant. These data establish the BiLDS technology as a sustained in vivo drug delivery platform that can localize protein and other growth factor release to a surgical site while providing a structural template for new tissue formation.Composting is a solid waste management alternative that avoids the emission of methane associated with its disposal in landfill and reduces or eliminates the need for chemical fertilisers if compost is applied. The main objective of this study was to analyse the environmental burdens of composting as a way to achieve a more circular valorisation of wine waste. To do so, with the purpose of identifying optimal operational conditions and determining the "hotspots" of the process, the life cycle assessment (LCA) methodology was used. The consumption of diesel fuel in machinery was determined to be the main critical point in the environmental effects of the system, followed by the transport and distribution of the compost. After the application of compost instead of mineral fertilisers, corn, tomato and strawberry crops would have a better environmental performance in most impact categories. In this sense, a maximum improvement of 65% in terrestrial ecotoxicity is achieved in strawberry cultivation. In light of the results obtained, it is demonstrated that composting is a suitable way of organic waste valorisation according to Circular Economy principles.Patients with congenital adrenal hyperplasia (CAH) are at risk of long-term cognitive and metabolic sequelae with some of the effects being attributed to the chronic glucocorticoid treatment that they receive. Our pilot study investigates genome-wide DNA methylation in patients with CAH to determine whether there is preliminary evidence for epigenomic reprogramming as well as any relationship to patient outcome. Here, we analysed CD4 + T cell DNA from 28 patients with CAH (mean age = 18.5 ± 6.5 years [y]) and 37 population controls (mean age = 17.0 ± 6.1 y) with the Infinium-HumanMethylation450 BeadChip array to measure genome-wide locus-specific DNA methylation levels. Effects of CAH, phenotype and CYP21A2 genotype on methylation were investigated as well as the association between differentially methylated CpGs and glucose homeostasis, blood lipid profile, and cognitive functions. In addition, we report data on a small cohort of 11 patients (mean age = 19.1, ±6.0 y) with CAH who were treated prenatally with cognitive and metabolic outcome in patients with CAH, although the data must be interpreted with caution due to the small sample size. Additional studies in larger cohorts are therefore warranted.Objective Sleep quality has a significant impact on human mental and physical health. The detection of sleep-wake states is thus of paramount importance in the study of sleep.  https://www.selleckchem.com/EGFR(HER).html  The gold standard method for sleep-wake classification is multi-sensor based polysomnography (PSG) which is normally recorded in clinical setting. The main drawbacks of PSG are the inconvenience to the subjects, the impact of discomfort on normal sleep cycles, and its requirement for experts\textquotesingle ~interpretation. In contrast, we aim to design an automated approach for sleep-wake classification using wearable fingertip photoplethysmographic (PPG) signal. Approach Time domain features are extracted from PPG and PPG based surrogate cardiac signal for sleep-wake classification. The minimal redundancy maximal relevance feature selection algorithm is employed to reduce irrelevant and redundant features. Main results Support vector machine (SVM) based supervised machine learning classifier is then used to classify sleep and wake states. The model is trained using 70\% events (6575 sleep-wake events) from the dataset, and the rest 30\% events (2818 sleep-wake events) are used for evaluating the performance of the model. Furthermore, the proposed model demonstrates a comparable performance (accuracy 81.10\%, sensitivity 81.06\%, specificity 82.50\%, precision 99.37\%, and F score 81.74\%) with respect to the existing uni-modal and multi-modal methods for sleep-wake classification. Significance This result advocates the potential of wearable PPG based sleep-wake classification. A wearable PPG based system would help in continuous, non-invasive monitoring of sleep quality.Background Conventional radiotherapy (RT) to pediatric brain tumors exposes a large volume of normal brain to unwarranted radiation causing late toxicity. We hypothesized that in well demarcated pediatric tumors lacking microscopic extensions, fractionated stereotactic RT (SRT), without target volume expansions, can reduce high dose normal tissue irradiation without affecting local control. Methods Between 2008 and 2017, fifty-two pediatric patients with brain tumors were treated using the CyberKnife (CK) with SRT in 180-200 cGy/fraction. Thirty representative cases were retrospectively planned for intensity modulated RT (IMRT) with 4-mm PTV expansion. We calculated the volume of normal tissue within the high or intermediate dose region adjacent to the target. Plan quality and radiation dose-volume dosimetry parameters were compared between CK and IMRT plans. We also reported overall survival (OS), progression-free survival (PFS) and local control (LC). Results Tumors included low-grade gliomas (n=28), craniopharyngiomas (n=16) and ependymomas (n=8).