Cisplatin is an effective chemotherapy drug that induces peripheral neuropathy in cancer patients. In rodent dorsal root ganglion neurons, cisplatin binds nuclear and mitochondrial DNA (mtDNA) inducing DNA damage and apoptosis. Platinum-mtDNA adducts inhibit mtDNA replication and transcription leading to mitochondrial degradation. Cisplatin also induces climbing deficiencies associated with neuronal apoptosis in adult Drosophila melanogaster. Here we used Drosophila larvae that express green fluorescent protein in the mitochondria of motor neurons to observe the effects of cisplatin on mitochondrial dynamics and function. Larvae treated with 10 μg/ml cisplatin had normal survival with deficiencies in righting and heat sensing behavior. Behavior was abrogated by, the pan caspase inhibitor, p35. However, active caspase 3 was not detected by immunostaining. There was a 27% decrease in mitochondrial membrane potential and a 42% increase in reactive oxygen species (ROS) in mitochondria along the axon. Examination of mitochondrial axonal trafficking showed no changes in velocity, flux or mitochondrial length. However, cisplatin treatment resulted in a greater number of stationary organelles caused by extended pausing during axonal motility. These results demonstrate that cisplatin induces behavior deficiencies in Drosophila larvae, decreased mitochondrial activity, increased ROS production and mitochondrial pausing without killing the larvae. Thus, we identified particular aspects of mitochondrial dynamics and function that are affected in cisplatin-induced peripheral neuropathy and may represent key therapeutic targets.
A malunited distal radius fracture can lead to symptomatic ulnar impaction syndrome, which is a common cause for ulnarsided wrist pain. If conservative treatment fails and symptoms persist after an arthroscopic ulnocarpal debridement, ulnar shortening osteotomy (USO) is the treatment of choice. Since the first USO described by Milch in 1941 after a malunited Colles fracture, many techniques have been described varying in surgical approach, type of osteotomy and osteosynthesis material used. Many studies demonstrated good to very good functional results after USO, reporting, however, a delayed union or non-union rate up to 18%. A modern, low profile, locking plate showed in our short-term study very good functional results and no implant-associated complications, in particular no non-union.
The Communication and Tracing App HIV (COMTRAC-HIV) project aims to develop a mobile health application for integrated care of HIV patients due to the low availability of those apps in Germany. This study addressed organizational conditions and necessary app functionalities, especially for the care of late diagnosed individuals (late presenters) and those using pre-exposure prophylaxis. We followed a human-centered design approach and interviewed HIV experts in Germany to describe the context of use of the app. The interviews were paraphrased and analyzed with a qualitative content analysis. To define the context of use, user group profiles were defined and tasks derived, which will represent the functionalities of the app. A total of eight experts were included in the study. The results show that the app should include a symptom diary for entering symptoms, side effects, and their intensity. It offers chat/video call functionality for communication with an HIV expert, appointment organization, and sharing findings. The app should also provide medication overview and reminders for medications and appointments. This qualitative study is a first step towards the development of an app for HIV individuals in Germany. Further research includes involving patients in the initial app design and test design usability.
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