[Peer counseling for amputations : A somewhat different instrument in trauma surgery]. / Peerberatungen bei Amputationen : Ein etwas anderes unfallchirurgisches Instrument.

The abrupt onset of the situation after a traumatic amputation and the preparatory discussions following unsuccessful attempts to preserve limbs with necessary amputation require a high level of empathy, attention and well-founded information individually tailored to the affected individuals. Optimization of the treatment process can only be achieved by considering these aspects.The self-motivation and cooperation of the patient should be encouraged. To achieve this goal, the professions involved are less suitable for counseling due to a lack of personal experience, whereas so-called peers, as knowledgeable and experienced advisors, are more appropriate. This insight can be derived from existing studies. Peer counseling has increasingly been integrated into routine treatment following amputations in trauma surgery, with positive effects. It is considered guideline-compliant therapy not only in rehabilitation. Against the background of long-standing legislation, especially the UN Convention on the Rights of Persons with Disabilities and the demands of those affected by amputation, the following presentation focuses on the instrumentalization and benefits of counseling. The structures of this particular counseling option, including regular training of counselors and established implementation, are currently not necessarily given but are continuously expanding and being adapted to needs. Concrete scientific evidence regarding measurable effects and positive impacts on outcomes is pending and are presented in a current research project.

Epigenomic profiling of non-small cell lung cancer xenografts uncover LRP12 DNA methylation as predictive biomarker for carboplatin resistance.

BACKGROUND: Non-small cell lung cancer (NSCLC) is the most common cause of cancer-related deaths worldwide and is primarily treated with radiation, surgery, and platinum-based drugs like cisplatin and carboplatin. The major challenge in the treatment of NSCLC patients is intrinsic or acquired resistance to chemotherapy. Molecular markers predicting the outcome of the patients are urgently needed. METHODS: Here, we employed patient-derived xenografts (PDXs) to detect predictive methylation biomarkers for platin-based therapies. We used MeDIP-Seq to generate genome-wide DNA methylation profiles of 22 PDXs, their parental primary NSCLC, and their corresponding normal tissues and complemented the data with gene expression analyses of the same tissues. Candidate biomarkers were validated with quantitative methylation-specific PCRs (qMSP) in an independent cohort. RESULTS: Comprehensive analyses revealed that differential methylation patterns are highly similar, enriched in PDXs and lung tumor-specific when comparing differences in methylation between PDXs versus primary NSCLC. We identified a set of 40 candidate regions with methylation correlated to carboplatin response and corresponding inverse gene expression pattern even before therapy. This analysis led to the identification of a promoter CpG island methylation of LDL receptor-related protein 12 (LRP12) associated with increased resistance to carboplatin. Validation in an independent patient cohort (n = 35) confirmed that LRP12 methylation status is predictive for therapeutic response of NSCLC patients to platin therapy with a sensitivity of 80% and a specificity of 84% (p < 0.01). Similarly, we find a shorter survival time for patients with LRP12 hypermethylation in the TCGA data set for NSCLC (lung adenocarcinoma). CONCLUSIONS: Using an epigenome-wide sequencing approach, we find differential methylation patterns from primary lung cancer and PDX-derived cancers to be very similar, albeit with a lower degree of differential methylation in primary tumors. We identify LRP12 DNA methylation as a powerful predictive marker for carboplatin resistance. These findings outline a platform for the identification of epigenetic therapy resistance biomarkers based on PDX NSCLC models.

Octopamine indirectly affects proboscis extension response habituation in Drosophila melanogaster by controlling sucrose responsiveness.

Octopamine is an important neurotransmitter in insects with multiple functions. Here, we investigated the role of this amine in a simple form of learning (habituation) in the fruit fly Drosophila melanogaster. Specifically, we asked if octopamine is necessary for normal habituation of a proboscis extension response (PER) to different sucrose concentrations. In addition, we analyzed the relationship between responsiveness to sucrose solutions applied to the tarsus and habituation of the proboscis extension response in the same individual. The Tyramine-ß-hydroxylase (Tßh) mutant lacks the enzyme catalyzing the final step of octopamine synthesis. This mutant was significantly less responsive to sucrose than controls. The reduced responsiveness directly led to faster habituation. Systemic application of octopamine or induction of octopamine synthesis by Tßh expression in a cluster of octopaminergic neurons within the suboesophageal ganglion restored sucrose responsiveness and habituation of octopamine mutants to control level. Further analyses imply that the reduced sucrose responsiveness of Tßh mutants is related to a lower sucrose preference, probably due to a changed carbohydrate metabolism, since Tßh mutants survived significantly longer under starved conditions. These findings suggest a pivotal role for octopamine in regulating sucrose responsiveness in fruit flies. Further, octopamine indirectly influences non-associative learning and possibly associative appetitive learning by regulating the evaluation of the sweet component of a sucrose reward.