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Kearns Ibrahim posted an update 6 months ago
Biosimilars are cheaper than original drugs and are thus of interest to the public. The aim of this article is to assess the benefits of introducing more than one biosimilar for the same substance (active pharmaceutical ingredient, API). The hypothesis is that the introduction of successive biosimilars of a specific original drug reduces the price of the selected API. The study focuses on drug prices varying with the successive arrival of new biosimilars. Three drugs that have at least three reimbursed biosimilars on the market were selected, two from the same therapeutic group (adalimumab and infliximab) and one (trastuzumab) representing another class of drugs. Danicamtiv in vivo The following data were analyzed price variation after the introduction of the first, second, and third biosimilar, and the average price reduction for all three biosimilars. Additionally, a literature review was conducted. The reimbursement of each new biosimilar is beneficial since it is associated with a price reduction in percentage terms. However, the first biosimilar brought about the greatest savings due to the higher initial prices of the original drugs and to Polish reimbursement rules. This article is helpful for when taking healthcare decisions regarding the pricing of and reimbursement for new biosimilars.Diffuse gliomas are a heterogeneous group of tumors with aggressive biological behavior and a lack of effective treatment methods. Despite new molecular findings, the differences between pathohistological types still require better understanding. In this in silico analysis, we investigated AKT1, AKT2, AKT3, CHUK, GSK3β, EGFR, PTEN, and PIK3AP1 as participants of EGFR-PI3K-AKT-mTOR signaling using data from the publicly available cBioPortal platform. Integrative large-scale analyses investigated changes in copy number aberrations (CNA), methylation, mRNA transcription and protein expression within 751 samples of diffuse astrocytomas, anaplastic astrocytomas and glioblastomas. The study showed a significant percentage of CNA in PTEN (76%), PIK3AP1 and CHUK (75% each), EGFR (74%), AKT2 (39%), AKT1 (32%), AKT3 (19%) and GSK3β (18%) in the total sample. Comprehensive statistical analyses show how genomics and epigenomics affect the expression of examined genes differently across various pathohistological types and grades, suggesting that genes AKT3, CHUK and PTEN behave like tumor suppressors, while AKT1, AKT2, EGFR, and PIK3AP1 show oncogenic behavior and are involved in enhanced activity of the EGFR-PI3K-AKT-mTOR signaling pathway. Our findings contribute to the knowledge of the molecular differences between pathohistological types and ultimately offer the possibility of new treatment targets and personalized therapies in patients with diffuse gliomas.Background and Objectives During intense training periods, there is a high need to monitor the external and especially the internal training load in order to fine-tune the training process and to avoid overreaching or overtraining. However, data on stress reactions, especially of biomarkers, to high training loads in children and youth are rare. Therefore, in this study, we aimed to investigate the training load of youth athletes during a training camp using a multilevel approach. Materials and Methods Six trained youth male cyclists performed a 7-day preseason training camp. To investigate the internal training load, every morning, minimally invasive “point-of-care testing” (POCT) devices were used to analyze the following biomarkers creatine kinase (CK), blood urea nitrogen (BUN), albumin (Alb), bilirubin (Bil), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total protein (TP). Additionally, data of training load measures (HR heart rate, RPE rating of perceived exertion, sRPE session- Alb are suitable for objectively quantifying the internal training load. The self-perception provides additional subjective information about the internal training load.The tomato leaf miner, Tuta absoluta is a destructive pest of tomato. The leaf-mining activities of its larvae can cause significant yield losses. Real-time quantitative polymerase chain reaction (RT-qPCR) is commonly used to measure gene expression, and the selection of stable reference genes for calibration and standardization is critical for accurate use of RT-qPCR. We studied the stable expression of nine common housekeeping genes in T. absoluta. These were examined at different developmental stages, in larval tissues, as well as those induced by exposure to 20E and insecticides. Four dedicated algorithms (geNorm, BestKeeper, NormFinder, and ΔCt method) and online tool (RefFinder) were used to analyze and rank the tested reference genes. Based on the standardized gene expression data of target gene ecdysone receptor (EcR), the applicability of specific reference genes was verified. The results clarify that the optimal internal reference genes vary greatly under different experimental conditions. GAPDH and RPS11 were the best reference genes for developmental stages; RPL28 and RPL10 for different tissues; EF1α and RPL28 for 20E treatment; EF1α and RPL7A for insecticide treatments. The most suitable reference genes in all experimental conditions are EF1α and RPL28.Some aquatic plants present high biomass production with serious consequences on ecosystem functioning. Such mass development can be favored by environmental factors. Temperature increases are expected to modify individual species responses that could shape future communities. We explored the impact of rising water temperature on the growth, phenology, and metabolism of six macrophytes belonging to two biogeographic origins (exotic, native) and two growth forms (submerged, emergent). From June to October, they were exposed to ambient temperatures and a 3 °C warming in outdoor mesocosms. Percent cover and canopy height were favored by warmer water for the exotic emergent Ludwigia hexapetala. Warming did not modify total final biomass for any of the species but led to a decrease in total soluble sugars for all, possibly indicating changes in carbon allocation. Three emergent species presented lower flavonol and anthocyanin contents under increased temperatures, suggesting lower investment in defense mechanisms and mitigation of the stress generated by autumn temperatures.