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  • Holck Norup posted an update 2 hours ago

    Adjusted logistic regression models showed an odds ratio of 1.37 ± 0.19 (CI 1.05, 1.80; p=.022) for the association of ALI-5 with perceived stress. This association was stronger in females (OR = 1.62 ± 0.28, CI 1.15, 2.28; p = .006) and did not significantly differ between age clusters. Results for the original ALI-10 score did not reach significance. The streamlined ALI-5 score seems to be a reliable risk score and is strongly associated with perceived stress in life. Longitudinal studies should further elaborate this association in different samples.Lay summary Stress from different sources can lead to serious diseases. A short composite index comprising of five medical variables is highly associated with perceived stress. This index is able to serve as an early indicator to detect people who are at risk to develop stress-related diseases.The diabetic foot ulcer (DFU) is a major disabling complication of diabetes mellitus. Growing evidence suggests that topical erythropoietin (EPO) can promote wound healing. The aim of this study is to clinically assess the efficacy of a proprietary topical EPO-containing hydrogel for treating DFUs. We conducted a randomized, controlled trial in 20 patients with DFUs. After a 14-day screening period, the DFUs of 20 eligible participants who fulfilled the inclusion criteria were randomly assigned (11) to either a 12-week of daily treatment with topical EPO and standard-of-care (SOC) or SOC treatment alone. The DFUs were assessed weekly until week 12. The primary outcome was 75% ulcer closure or higher. After 12 weeks of treatment, 75% ulcer closure was achieved in 6 of the 10 patients whose DFUs were treated with topical EPO and in one of the 8 patients whose DFUs were treated with SOC alone. The mean area of the DFUs that were treated with topical EPO and SOC was significantly smaller than those treated with SOC alone (1.2 ± 1.4 cm2 vs. 4.2 ± 3.4 cm2; p = 0.023). Re-epithelialization was faster in the topically EPO-treated DFUs than in the SOC-treated DFUs. There were no treatment-related adverse events. Ivosidenib We conclude that topical EPO is a promising treatment for promoting the healing of DFUs. Clinical Trial Registration number NCT02361931.Amygdalin has been promoted as an alternative cancer cure. However, it is still unclear how this cyanogenic glycoside affects non-cancer cells including bone cells. This study first investigated the impact of amygdalin on viability, morphology and expression of important genes in human osteoblasts in vitro. Primary human osteoblast cultures were exposed to amygdalin at concentrations 0; 0.1; 1 and 10 mg/mL in growth medium for 72 h. Cell viability, osteoblasts morphology and expression of 10 genes associated with osteoblast-specific pathways, oxidative stress and cell death were determined. Osteoblasts viability was significantly decreased (-27.26%) and their size was reduced (-23.20%) at the highest concentration of amygdalin (10 mg/mL). This concentration of amygdalin down-regulated the expression of COL1A1 and ALPL genes, whereas the expression of BGLAP, TNFSF11 and WNT5A genes was increased. The osteoblast cultivation with 0.1 mg/mL amygdalin caused down-regulation of COL1A1 gene. No changes in expression were determined for RUNX2, BAX, CASP1, SOD1 and GPX1 genes among all tested concentrations of amygdalin. In conclusion, amygdalin in a high concentration negatively affected mineralization of extracellular matrix, increased bone resorption and decreased osteoblast viability. These changes were accompanied by modified expression profiles of responsible genes.Oncolytic viruses (OVs) are novel cancer gene therapies that are moving toward the forefront of modern medicines. However, their full therapeutic potential is hindered by the lack of convenient and reliable strategies to visualize and quantify OV growth kinetics and therapeutic efficacy in live cells. In this study, we present an innovative imaging approach for single-cell real-time analysis of OV replication and efficacy in cancer cells. We selected SG33 as a prototypic new OV that derives from wild-type Myxoma virus (MYXV). Lausanne Toulouse 1 (T1) was used as control. We equipped SG33 and T1 genomes with the ANCHOR system and infected a panel of cell lines. The ANCHOR system is composed of a fusion protein (OR-GFP) that specifically binds to a short nonrepetitive DNA target sequence (ANCH) and spreads onto neighboring sequences by protein oligomerization. Its accumulation on the tagged viral DNA results in the creation of fluorescent foci. We found that (1) SG33 and T1-ANCHOR DNA can be readily detected and quantified by live imaging, (2) both OVs generate perinuclear replication foci after infection clustering into horse-shoe shape replication centers, and (3) SG33 replicates to higher levels as compared with T1. Lastly, as a translational proof of concept, we benchmarked SG33 replication and oncolytic efficacy in primary cancer cells derived from pancreatic adenocarcinoma (PDAC) both at the population and at the single-cell levels. In vivo, SG33 significantly replicates in experimental tumors to inhibit tumor growth. Collectively, we provide herein for the first time a novel strategy to quantify each step of OV infection in live cells and in real time by tracking viral DNA and provide first evidence of theranostic strategies for PDAC patients. Thus, this approach has the potential to rationalize the use of OVs for the benefit of patients with incurable diseases.Responsible science is mandatory for every research institution. As economic challenges, fast evolving technologies and competitiveness impact drastically the scientific productivity and quality, institutions must take action. Research core facilities using animal models (CORE) are central in biomedical institutions. Therefore, building a strong CORE represents a priority for research organizations. More precisely, COREs must define their purpose, ensure proper long term resources and promote ethics and transparency. The heads of COREs play, as managers, a key role in the development and in the coordination of all activities. They deal with multiple challenges, such as divergent objectives, heavy workload and limited resources, exposing them to psychosocial risks, and might compromise their ability to react rationally to the pressure. The implementation of a culture of care and of social responsibility is essential for COREs and for their institutions. In this, the collaborative efforts between institutions’ officials, administrative staff and scientists allow the support of CORE decisions, the development of innovative tools and the promotion of a responsible science.