Design and Implementation of a Cross- Platform Application for Internet- and Mobile-Based Interventions

For internet based interventions having noticeable impacts on the mental health of patients, the usage of these IBIs is expanding. Following this trend, the Institute of Psychology and Education, Department of Clinical Psychology and Psychotherapy at Ulm University (KLIPS) want to use these for research purposes. Offered tools of other suppliers do not fit for the use of KLIPS as they are lacking needed features and flexibility. They either do not provide the ability to create and use own interventions, are expensive to use or do not provide enough flexibility as needed by KLIPS. Hence, the goal is to create a software system covering the needed requirements to offer the ability to support the institute’s research. To provide even easier access to IBIs for patients, the software system should follow the concept of Internet and Mobile based Interventions (IMI). The outcome expected in terms of user acceptance and results of the treatment are even higher due to the usage of the IMI concept. For this purpose, a plan for a software system was created to provide the support described above. The software system should offer the ability to create and manage IBIs and to guide and observe the patients participating in them. For easier development and handling, the system was planned to be split into four different parts, each of them described more precisely. Each part will be developed separately but all parts will work together to build one big functional software system

The p53 binding protein PDCD5 is not rate-limiting in DNA damage induced cell death

The tumour suppressor p53 is an important mediator of cell cycle arrest and apoptosis in response to DNA damage, acting mainly by transcriptional regulation of specific target genes. The exact details how p53 modulates this decision on a molecular basis is still incompletely understood. One mechanism of regulation is acetylation of p53 on lysine K120 by the histone-acetyltransferase Tip60, resulting in preferential transcription of proapoptotic target genes. PDCD5, a protein with reported pro-apoptotic function, has recently been identified as regulator of Tip60-dependent p53-acetylation. In an effort to clarify the role of PDCD5 upon DNA damage, we generated cell lines in which PDCD5 expression was conditionally ablated by shRNAs and investigated their response to genotoxic stress. Surprisingly, we failed to note a rate-limiting role of PDCD5 in the DNA damage response. PDCD5 was dispensable for DNA damage induced apoptosis and cell cycle arrest and we observed no significant changes in p53 target gene transcription. While we were able to confirm interaction of PDCD5 with p53, we failed to do so for Tip60. Altogether, our results suggest a role of PDCD5 in the regulation of p53 function but unrelated to cell cycle arrest or apoptosis, at least in the cell types investigated.FP06 RTN ‘ApopTrain’Tyrolean Science FundKrebshilfe-Tyro

Circulating miRNAs in bone health and disease

microRNAs have evolved as important regulators of multiple biological pathways essential for bone homeostasis, and microRNA research has furthered our understanding of the mechanisms underlying bone health and disease. This knowledge, together with the finding that active or passive release of microRNAs from cells into the extracellular space enables minimal-invasive detection in biofluids (circulating miRNAs), motivated researchers to explore microRNAs as biomarkers in several pathologic conditions, including bone diseases. Thus, exploratory studies in cohorts representing different types of bone diseases have been performed. In this review, we first summarize important molecular basics of microRNA function and release and provide recommendations for best (pre-)analytical practices and documentation standards for circulating microRNA research required for generating high quality data and ensuring reproducibility of results. Secondly, we review how the genesis of bone-derived circulating microRNAs via release from osteoblasts and osteoclasts could contribute to the communication between these cells. Lastly, we summarize evidence from clinical research studies that have investigated the clinical utility of microRNAs as biomarkers in musculoskeletal disorders. While previous reviews have mainly focused on diagnosis of primary osteoporosis, we have also included studies exploring the utility of circulating microRNAs in monitoring anti-osteoporotic treatment and for diagnosis of other types of bone diseases, such as diabetic osteopathy, bone degradation in inflammatory diseases, and monogenetic bone diseases.Peer reviewe

Fashion “see-now-buy-now”: implications and process adaptations

Purpose: The purpose of this paper is to identify if and how the see-now-buy-now model impacts the traditional buying, merchandising and supply chain processes (BMSCP) of multi-brand fashion retailers (MBFR) and whether they need to be adapted in order to facilitate this development. Design/methodology/approach: This exploratory study includes three industry case studies, triangulated with external observers. A total of 11 semi-structured interviews were conducted within Germany and the UK. Findings: Findings demonstrate that in order to adopt the see-now-buy-now model there is a need for process-shortening, as well as better process and network alignment between MBFR and brands through agility, supplier–relationship management and vertical integration in order to stay competitive against time-based competition. Whilst most steps of the traditional BMSCP are still applicable under the see-now-buy-now model, they must be re-engineered and shortened, with the steps being rolling rather than linear, with buyers and merchandisers operating in a more hybrid role. Originality/value: This paper addresses the lack of research on the see-now-buy-now model as well as on the BMSCP of MBFR and the implications that see-now-buy-now could have on those processes. A modified buying, merchandising and supply chain framework adapted to incorporate see-now-buy-now is created which will be useful for academics and practitioners

Overweight/obesity as the potentially most important lifestyle factor associated with signs of pneumonia in COVID-19

Objective: The occurrence of pneumonia separates severe cases of COVID-19 from the majority of cases with mild disease. However, the factors determining whether or not pneumonia develops remain to be fully uncovered. We therefore explored the associations of several lifestyle factors with signs of pneumonia in COVID-19. Methods Between May and July 2020, we conducted an online survey of 201 adults in Germany who had recently gone through COVID-19, predominantly as outpatients. Of these, 165 had a PCR-based diagnosis and 36 had a retrospective diagnosis by antibody testing. The survey covered demographic information, eight lifestyle factors, comorbidities and medication use. We defined the main outcome as the presence vs. the absence of signs of pneumonia, represented by dyspnea, the requirement for oxygen therapy or intubation. Results: Signs of pneumonia occurred in 39 of the 165 individuals with a PCR-based diagnosis of COVID-19 (23.6%). Among the lifestyle factors examined, only overweight/obesity was associated with signs of pneumonia (odds ratio 2.68 (1.29-5.59) p = 0.008). The observed association remained significant after multivariate adjustment, with BMI as a metric variable, and also after including the antibody-positive individuals into the analysis. Conclusions: This exploratory study finds an association of overweight/obesity with signs of pneumonia in COVID-19. This finding suggests that a signal proportional to body fat mass, such as the hormone leptin, impairs the body's ability to clear SARS-CoV-2 before pneumonia develops. This hypothesis concurs with previous work and should be investigated further to possibly reduce the proportion of severe cases of COVID-19

Ferritin H deficiency deteriorates cellular iron handling and worsens Salmonella typhimurium infection by triggering hyperinflammation

Iron is an essential nutrient for mammals as well as for pathogens. Inflammation-driven changes in systemic and cellular iron homeostasis are central for host-mediated antimicrobial strategies. Here, we studied the role of the iron storage protein ferritin H (FTH) for the control of infections with the intracellular pathogen Salmonella enterica serovar Typhimurium by macrophages. Mice lacking FTH in the myeloid lineage (LysM-Cre+/+Fthfl/fl mice) displayed impaired iron storage capacities in the tissue leukocyte compartment, increased levels of labile iron in macrophages, and an accelerated macrophage-mediated iron turnover. While under steady-state conditions, LysM-Cre+/+Fth+/+ and LysM-Cre+/+Fthfl/fl animals showed comparable susceptibility to Salmonella infection, i.v. iron supplementation drastically shortened survival of LysM-Cre+/+Fthfl/fl mice. Mechanistically, these animals displayed increased bacterial burden, which contributed to uncontrolled triggering of NF-κB and inflammasome signaling and development of cytokine storm and death. Importantly, pharmacologic inhibition of the inflammasome and IL-1β pathways reduced cytokine levels and mortality and partly restored infection control in iron-treated ferritin-deficient mice. These findings uncover incompletely characterized roles of ferritin and cellular iron turnover in myeloid cells in controlling bacterial spread and for modulating NF-κB and inflammasome-mediated cytokine activation, which may be of vital importance in iron-overloaded individuals suffering from severe infections and sepsis

Hypoxia induced downregulation of hepcidin is mediated by platelet derived growth factor BB

OBJECTIVE: Hypoxia affects body iron homeostasis; however, the underlying mechanisms are incompletely understood. DESIGN: Using a standardised hypoxia chamber, 23 healthy volunteers were subjected to hypoxic conditions, equivalent to an altitude of 5600 m, for 6 h. Subsequent experiments were performed in C57BL/6 mice, CREB-H knockout mice, primary hepatocytes and HepG2 cells. RESULTS: Exposure of subjects to hypoxia resulted in a significant decrease of serum levels of the master regulator of iron homeostasis hepcidin and elevated concentrations of platelet derived growth factor (PDGF)-BB. Using correlation analysis, we identified PDGF-BB to be associated with hypoxia mediated hepcidin repression in humans. We then exposed mice to hypoxia using a standardised chamber and observed downregulation of hepatic hepcidin mRNA expression that was paralleled by elevated serum PDGF-BB protein concentrations and higher serum iron levels as compared with mice housed under normoxic conditions. PDGF-BB treatment in vitro and in vivo resulted in suppression of both steady state and BMP6 inducible hepcidin expression. Mechanistically, PDGF-BB inhibits hepcidin transcription by downregulating the protein expression of the transcription factors CREB and CREB-H, and pharmacological blockade or genetic ablation of these pathways abrogated the effects of PDGF-BB toward hepcidin expression. CONCLUSIONS: Hypoxia decreases hepatic hepcidin expression by a novel regulatory pathway exerted via PDGF-BB, leading to increased availability of circulating iron that can be used for erythropoiesis

Driving chronicity in rheumatoid arthritis: perpetuating role of myeloid cells

Acute inflammation is a complex and tightly regulated homeostatic process that includes leukocyte migration from the vasculature into tissues to eliminate the pathogen/injury, followed by a pro-resolving response promoting tissue repair. However, if inflammation is uncontrolled as in chronic diseases such as Rheumatoid Arthritis (RA) it leads to tissue damage and disability. Synovial tissue inflammation in RA patients is maintained by sustained activation of multiple inflammatory positive-feedback regulatory pathways in a variety of cells including myeloid cells. In this review, we will highlight recent evidence uncovering biological mechanisms contributing to the aberrant activation of myeloid cells that contributes to perpetuation of inflammation in RA, and discuss emerging data on anti-inflammatory mediators contributing to sustained remission that may inform a novel category of therapeutic targets