TY - JOUR A1 - Warschburger, Petra A1 - Petersen, Ann-Christin A1 - von Rezori, Roman Enzio A1 - Buchallik, Friederike A1 - Baumeister, Harald A1 - Holl, Reinhard A1 - Minden, Kirsten A1 - Müller-​Stierlin, Annabel Sandra A1 - Reinauer, Christina A1 - Staab, Doris A1 - COACH consortium, T1 - A prospective investigation of developmental trajectories of psychosocial adjustment in adolescents facing a chronic condition - study protocol of an observational, multi-center study JF - BMC Pediatrics N2 - Background Relatively little is known about protective factors and the emergence and maintenance of positive outcomes in the field of adolescents with chronic conditions. Therefore, the primary aim of the study is to acquire a deeper understanding of the dynamic process of resilience factors, coping strategies and psychosocial adjustment of adolescents living with chronic conditions. Methods/design We plan to consecutively recruit N = 450 adolescents (12–21 years) from three German patient registries for chronic conditions (type 1 diabetes, cystic fibrosis, or juvenile idiopathic arthritis). Based on screening for anxiety and depression, adolescents are assigned to two parallel groups – “inconspicuous” (PHQ-9 and GAD-7 < 7) vs. “conspicuous” (PHQ-9 or GAD-7 ≥ 7) – participating in a prospective online survey at baseline and 12-month follow-up. At two time points (T1, T2), we assess (1) intra- and interpersonal resiliency factors, (2) coping strategies, and (3) health-related quality of life, well-being, satisfaction with life, anxiety and depression. Using a cross-lagged panel design, we will examine the bidirectional longitudinal relations between resiliency factors and coping strategies, psychological adaptation, and psychosocial adjustment. To monitor Covid-19 pandemic effects, participants are also invited to take part in an intermediate online survey. Discussion The study will provide a deeper understanding of adaptive, potentially modifiable processes and will therefore help to develop novel, tailored interventions supporting a positive adaptation in youths with a chronic condition. These strategies should not only support those at risk but also promote the maintenance of a successful adaptation. Trial registration German Clinical Trials Register (DRKS), no. DRKS00025125. Registered on May 17, 2021. KW - Chronic conditions KW - Adolescents KW - Prospective KW - Quality of life KW - Resiliency KW - Coping KW - Protective factors KW - Type 1 diabetes KW - Juvenile idiopathic arthritis KW - Cystic fibrosis Y1 - 2021 U6 - https://doi.org/10.1186/s12887-021-02869-9 SN - 1471-2431 VL - 21 SP - 1 EP - 13 PB - BMC pediatrics CY - London ER - TY - GEN A1 - Warschburger, Petra A1 - Petersen, Ann-Christin A1 - von Rezori, Roman Enzio A1 - Buchallik, Friederike A1 - Baumeister, Harald A1 - Holl, Reinhard A1 - Minden, Kirsten A1 - Müller-​Stierlin, Annabel Sandra A1 - Reinauer, Christina A1 - Staab, Doris A1 - COACH consortium, T1 - A prospective investigation of developmental trajectories of psychosocial adjustment in adolescents facing a chronic condition - study protocol of an observational, multi-center study T2 - Zweitveröffentlichungen der Universität Potsdam : Humanwissenschaftliche Reihe N2 - Background Relatively little is known about protective factors and the emergence and maintenance of positive outcomes in the field of adolescents with chronic conditions. Therefore, the primary aim of the study is to acquire a deeper understanding of the dynamic process of resilience factors, coping strategies and psychosocial adjustment of adolescents living with chronic conditions. Methods/design We plan to consecutively recruit N = 450 adolescents (12–21 years) from three German patient registries for chronic conditions (type 1 diabetes, cystic fibrosis, or juvenile idiopathic arthritis). Based on screening for anxiety and depression, adolescents are assigned to two parallel groups – “inconspicuous” (PHQ-9 and GAD-7 < 7) vs. “conspicuous” (PHQ-9 or GAD-7 ≥ 7) – participating in a prospective online survey at baseline and 12-month follow-up. At two time points (T1, T2), we assess (1) intra- and interpersonal resiliency factors, (2) coping strategies, and (3) health-related quality of life, well-being, satisfaction with life, anxiety and depression. Using a cross-lagged panel design, we will examine the bidirectional longitudinal relations between resiliency factors and coping strategies, psychological adaptation, and psychosocial adjustment. To monitor Covid-19 pandemic effects, participants are also invited to take part in an intermediate online survey. Discussion The study will provide a deeper understanding of adaptive, potentially modifiable processes and will therefore help to develop novel, tailored interventions supporting a positive adaptation in youths with a chronic condition. These strategies should not only support those at risk but also promote the maintenance of a successful adaptation. Trial registration German Clinical Trials Register (DRKS), no. DRKS00025125. Registered on May 17, 2021. T3 - Zweitveröffentlichungen der Universität Potsdam : Humanwissenschaftliche Reihe - 762 KW - Chronic conditions KW - Adolescents KW - Prospective KW - Quality of life KW - Resiliency KW - Coping KW - Protective factors KW - Type 1 diabetes KW - Juvenile idiopathic arthritis KW - Cystic fibrosis Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-549951 SN - 1866-8364 VL - 21 SP - 1 EP - 13 PB - Universitätsverlag Potsdam CY - Potsdam ER - TY - JOUR A1 - Kosztolowicz, Tadeusz A1 - Metzler, Ralf A1 - Wąsik, Slawomir A1 - Arabski, Michal T1 - Modelling experimentally measured of ciprofloxacin antibiotic diffusion in Pseudomonas aeruginosa biofilm formed in artificial sputum medium JF - PLoS ONE N2 - We study the experimentally measured ciprofloxacin antibiotic diffusion through a gel-like artificial sputum medium (ASM) mimicking physiological conditions typical for a cystic fibrosis layer, in which regions occupied by Pseudomonas aeruginosa bacteria are present. To quantify the antibiotic diffusion dynamics we employ a phenomenological model using a subdiffusion-absorption equation with a fractional time derivative. This effective equation describes molecular diffusion in a medium structured akin Thompson’s plumpudding model; here the ‘pudding’ background represents the ASM and the ‘plums’ represent the bacterial biofilm. The pudding is a subdiffusion barrier for antibiotic molecules that can affect bacteria found in plums. For the experimental study we use an interferometric method to determine the time evolution of the amount of antibiotic that has diffused through the biofilm. The theoretical model shows that this function is qualitatively different depending on whether or not absorption of the antibiotic in the biofilm occurs. We show that the process can be divided into three successive stages: (1) only antibiotic subdiffusion with constant biofilm parameters, (2) subdiffusion and absorption of antibiotic molecules with variable biofilm transport parameters, (3) subdiffusion and absorption in the medium but the biofilm parameters are constant again. Stage 2 is interpreted as the appearance of an intensive defence build–up of bacteria against the action of the antibiotic, and in the stage 3 it is likely that the bacteria have been inactivated. Times at which stages change are determined from the experimentally obtained temporal evolution of the amount of antibiotic that has diffused through the ASM with bacteria. Our analysis shows good agreement between experimental and theoretical results and is consistent with the biologically expected biofilm response. We show that an experimental method to study the temporal evolution of the amount of a substance that has diffused through a biofilm is useful in studying the processes occurring in a biofilm. We also show that the complicated biological process of antibiotic diffusion in a biofilm can be described by a fractional subdiffusion-absorption equation with subdiffusion and absorption parameters that change over time. KW - Bacterial biofilms KW - Antibiotics KW - Biofilms KW - Cystic fibrosis KW - Absorption KW - Pseudomonas aeruginosa KW - Sputum KW - Biological defense mechanisms Y1 - 2020 U6 - https://doi.org/10.1371/journal.pone.0243003 SN - 1932-6203 VL - 15 PB - PLOS CY - San Francisco, California, US ER - TY - GEN A1 - Kosztolowicz, Tadeusz A1 - Metzler, Ralf A1 - Wąsik, Slawomir A1 - Arabski, Michal T1 - Modelling experimentally measured of ciprofloxacin antibiotic diffusion in Pseudomonas aeruginosa biofilm formed in artificial sputum medium T2 - Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe N2 - We study the experimentally measured ciprofloxacin antibiotic diffusion through a gel-like artificial sputum medium (ASM) mimicking physiological conditions typical for a cystic fibrosis layer, in which regions occupied by Pseudomonas aeruginosa bacteria are present. To quantify the antibiotic diffusion dynamics we employ a phenomenological model using a subdiffusion-absorption equation with a fractional time derivative. This effective equation describes molecular diffusion in a medium structured akin Thompson’s plumpudding model; here the ‘pudding’ background represents the ASM and the ‘plums’ represent the bacterial biofilm. The pudding is a subdiffusion barrier for antibiotic molecules that can affect bacteria found in plums. For the experimental study we use an interferometric method to determine the time evolution of the amount of antibiotic that has diffused through the biofilm. The theoretical model shows that this function is qualitatively different depending on whether or not absorption of the antibiotic in the biofilm occurs. We show that the process can be divided into three successive stages: (1) only antibiotic subdiffusion with constant biofilm parameters, (2) subdiffusion and absorption of antibiotic molecules with variable biofilm transport parameters, (3) subdiffusion and absorption in the medium but the biofilm parameters are constant again. Stage 2 is interpreted as the appearance of an intensive defence build–up of bacteria against the action of the antibiotic, and in the stage 3 it is likely that the bacteria have been inactivated. Times at which stages change are determined from the experimentally obtained temporal evolution of the amount of antibiotic that has diffused through the ASM with bacteria. Our analysis shows good agreement between experimental and theoretical results and is consistent with the biologically expected biofilm response. We show that an experimental method to study the temporal evolution of the amount of a substance that has diffused through a biofilm is useful in studying the processes occurring in a biofilm. We also show that the complicated biological process of antibiotic diffusion in a biofilm can be described by a fractional subdiffusion-absorption equation with subdiffusion and absorption parameters that change over time. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 1107 KW - Bacterial biofilms KW - Antibiotics KW - Biofilms KW - Cystic fibrosis KW - Pseudomonas aeruginosa KW - Sputum KW - Biological defense mechanisms Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-490866 SN - 1866-8372 IS - 1107 ER - TY - JOUR A1 - Becker, Katrin Anne A1 - Riethmueller, Joachim A1 - Seitz, Aaron P. A1 - Gardner, Aaron A1 - Boudreau, Ryan A1 - Kamler, Markus A1 - Kleuser, Burkhard A1 - Schuchman, Edward A1 - Caldwell, Charles C. A1 - Edwards, Michael J. A1 - Grassme, Heike A1 - Brodlie, Malcolm A1 - Gulbins, Erich T1 - Sphingolipids as targets for inhalation treatment of cystic fibrosis JF - Advanced drug delivery reviews N2 - Studies over the past several years have demonstrated the important role of sphingolipids in cystic fibrosis (CF), chronic obstructive pulmonary disease and acute lung injury. Ceramide is increased in airway epithelial cells and alveolar macrophages of CF mice and humans, while sphingosine is dramatically decreased. This increase in ceramide results in chronic inflammation, increased death of epithelial cells, release of DNA into the bronchial lumen and thereby an impairment of mucociliary clearance; while the lack of sphingosine in airway epithelial cells causes high infection susceptibility in CF mice and possibly patients. The increase in ceramide mediates an ectopic expression of beta 1-integrins in the luminal membrane of CF epithelial cells, which results, via an unknown mechanism, in a down-regulation of acid ceramidase. It is predominantly this down-regulation of acid ceramidase that results in the imbalance of ceramide and sphingosine in CF cells. Correction of ceramide and sphingosine levels can be achieved by inhalation of functional acid sphingomyelinase inhibitors, recombinant acid ceramidase or by normalization of beta 1-integrin expression and subsequent re-expression of endogenous acid ceramidase. These treatments correct pulmonary inflammation and prevent or treat, respectively, acute and chronic pulmonary infections in CF mice with Staphylococcus aureus and mucoid or non-mucoid Pseudomonas aeruginosa. Inhalation of sphingosine corrects sphingosine levels only and seems to mainly act against the infection. Many antidepressants are functional inhibitors of the acid sphingomyelinase and were designed for systemic treatment of major depression. These drugs could be repurposed to treat CF by inhalation. KW - Ceramide KW - Acid sphingomyelinase KW - Cystic fibrosis KW - COPD KW - Inhalation Y1 - 2018 U6 - https://doi.org/10.1016/j.addr.2018.04.015 SN - 0169-409X SN - 1872-8294 VL - 133 SP - 66 EP - 75 PB - Elsevier CY - Amsterdam ER -