Extracellular heat shock protein 70 levels in tumour-bearing dogs and cats treated with radiation therapy and hyperthermia

Hyperthermia is a form of a cancer treatment which is frequently applied in combination with radiotherapy (RT) to improve therapy responses and radiosensitivity. The mode of action of hyperthermia is multifactorial; the one hand by altering the amount of the blood circulation in the treated tissue, on the other hand by modulating molecular pathways involved in cell survival processes and immunogenic interactions. One of the most dominant proteins induced by hyperthermia is the major stress-inducible heat shock protein 70 (Hsp70). Hsp70 can be found in the blood either as a free-protein (free HSP70) derived from necrotic cells, or lipid-bound (liposomal Hsp70) when it is actively released in extracellular vesicles (EVs) by living cells. The aim of the study was to evaluate the levels of free and liposomal Hsp70 before and after treatment with RT alone or hyperthermia combined with radiotherapy (HTRT) in dogs and cats to evaluate therapy responses. Peripheral blood was collected from feline and canine patients before and at 2, 4, 6 and 24 h after treatment with RT or HTRT. Hsp70 enzyme-linked immunosorbent assays (ELISAs) were performed to determine the free and liposomal Hsp70 concentrations in the serum. The levels were analysed after the first fraction of radiation to study immediate effects and after all applied fractions to study cumulative effects. The levels of free and liposomal Hsp70 levels in the circulation were not affected by the first singular treatment and cumulative effects of RT in cats however, after finalizing all treatment cycles with HTRT free and liposomal Hsp70 levels significantly increased. In dogs, HTRT, but not treatment with RT alone, significantly affected liposomal Hsp70 levels during the first fraction. Free Hsp70 levels were significantly increased after RT, but not HTRT, during the first fraction in dogs. In dogs, on the other hand, RT alone resulted in a significant increase in liposomal Hsp70, but HTRT did not significantly affect the liposomal Hsp70 when cumulative effects were analysed. Free Hsp70 was significantly induced in dogs after both, RT and HTRT when cumulative effects were analysed. RT and HTRT treatments differentially affect the levels of free and liposomal Hsp70 in dogs and cats. Both forms of Hsp70 could potentially be further investigated as potential liquid biopsy markers to study responses to RT and HTRT treatment in companion animals

Über den Tellerrand hinaus: Studierende positiv gegenüber visionären Wahlcurricula im Medizinstudium eingestellt

Objective: Space for personality development as well as for the development of critical, creative and interdisciplinary thinking is rarely found in medical curricula in Germany. To be prepared for the challenges of modern medicine, future physicians need a visionary mindset. The aim of this study is to determine the need for teaching such content among medical students in the context of visionary elective curricula and to examine these with regard to the desired topics and organizational structure.Methods: This is a cross-sectional study with 236 medical students from all semesters of the Ludwig-Maximilians-University Munich. The survey consists of 50 questions and includes single choice, multiple choice, matrix questions, open-ended questions and Likert scales. Responses were examined using descriptive statistics and compared parametrically in sub-aspects.Results: Three-quarters of respondents would like to see curricular content on interdisciplinary interfaces with other disciplines. A suitable framework for this is seen by 87% of the respondents in a visionary elective curriculum. Students would like to see a broad range of specific content such as global health, politics, business, and computer science. The majority of respondents would like to see 1 unit of instruction per week and would participate in an appropriate program. Such an offering would promote creative (53.6%), critical (63.7%), and interdisciplinary thinking (69.0%) and train to become better physicians (87%).Conclusion: Participants in this study are positive toward the introduction of visionary content in medical school. Faculties should build visionary elective curricula according to the graduate profile requirements of the new NKLM 2.0 to make medical education sustainable.Zielsetzung: Platz für Persönlichkeitsbildung sowie für die Entwicklung kritischen, kreativen und interdisziplinären Denkens findet sich nur selten in medizinischen Curricula in Deutschland. Um auf die Herausforderungen der modernen Medizin vorbereitet zu sein, brauchen angehende Ärztinnen/Ärzte eine visionäre Geisteshaltung. Ziel der Studie ist es, den Bedarf für die Vermittlung solcher Inhalte unter Medizinstudierenden im Rahmen von visionären Wahlcurricula zu ermitteln und diese hinsichtlich der gewünschten inhaltlichen und organisatorischen Struktur zu untersuchen.Methodik: Es handelt sich um eine Querschnittstudie mit 236 Medizinstudierenden aus allen Semestern der Ludwig-Maximilians-Universität München. Die Umfrage besteht aus 50 Fragen und beinhaltet Single-Choice, Multiple Choice, Matrixfragen, offene Fragen und Likert-Skalen. Die Antworten wurden mittels deskriptiver Statistik untersucht und in Teilaspekten parametrisch verglichen.Ergebnisse: Dreiviertel der Befragten wünschen sich curriculare Inhalte zu interdisziplinären Schnittstellen mit anderen Fachrichtungen. Ein geeigneter Rahmen dafür wird von 87% der Befragten in einem visionären Wahlcurriculum gesehen. Die Studierenden wünschen sich ein breites Angebot spezifischer Inhalte wie Global Health, Politik, Wirtschaft und Informatik. Die Mehrheit der Befragten wünscht sich einen Zeitumfang von 1 Unterrichtseinheit pro Woche und würde an einem entsprechenden Programm teilnehmen. Ein solches Angebot würde das kreative (53,6%), kritische (63,7%) und interdisziplinäre Denken (69,0%) fördern und zu besseren Ärztinnen/Ärzten ausbilden (87%).Schlussfolgerung: Die Teilnehmenden dieser Studie sind gegenüber der Einführung visionärer Inhalte im Medizinstudium positiv eingestellt. Fakultäten sollten entsprechend der Anforderungen des Absolventenprofils des neuen NKLM 2.0 visionäre Wahlcurricula aufbauen, um die Ausbildung von Ärztinnen und Ärzten zukunftsfähig zu machen

Coronin 1A, a novel player in integrin biology, controls neutrophil trafficking in innate immunity

Trafficking of polymorphonuclear neutrophils (PMNs) during inflammation critically depends on the beta(2) integrins lymphocyte function-associated antigen 1 (LFA-1) (CD11a/CD18) and macrophage-1 antigen (CD11b/CD18). Here, we identify coronin 1A (Coro1A) as a novel regulator of beta(2) integrins that interacts with the cytoplasmic tail of CD18 and is crucial for induction of PMN adhesion and postadhesion events, including adhesion strengthening, spreading, and migration under flow conditions. Transition of PMN rolling to firm adhesion critically depends on Coro1A by regulating the accumulation of high-affinity LFA-1 in focal zones of adherent cells. Defective integrin affinity regulation in the genetic absence of Coro1A impairs leukocyte adhesion and extravasation in inflamed cremaster muscle venules in comparison with control animals. In a Helicobacter pylori mouse infection model, PMN infiltration into the gastric mucosa is dramatically reduced in Coro1A(-/-) mice, resulting in an attenuated gastric inflammation. Thus, Coro1A represents an important novel player in integrin biology, with key functions in PMN trafficking during innate immunity