Search

Supplemental material, sj-pdf-7-jcb-10.1177_0271678X231168499 for Zfp580 inactivation as a new therapeutic target to enhance recovery after stroke in mice by Christian J Hoffmann, Melanie TC Kuffner, Leif Koschützke, Stephanie Lorenz, Janet Lips, Philipp Boehm-Sturm, Susanne Mueller, Stefan P Koch, Jeehye An, Lucius S Fekonja, Polina Bugaeva, Andre Rex, Gisela Lättig Tünnemann, Matthias Endres and Christoph Harms in Journal of Cerebral Blood Flow & Metabolism

Supplemental material, sj-pdf-6-jcb-10.1177_0271678X231168499 for Zfp580 inactivation as a new therapeutic target to enhance recovery after stroke in mice by Christian J Hoffmann, Melanie TC Kuffner, Leif Koschützke, Stephanie Lorenz, Janet Lips, Philipp Boehm-Sturm, Susanne Mueller, Stefan P Koch, Jeehye An, Lucius S Fekonja, Polina Bugaeva, Andre Rex, Gisela Lättig Tünnemann, Matthias Endres and Christoph Harms in Journal of Cerebral Blood Flow & Metabolism

Supplemental material, sj-pdf-8-jcb-10.1177_0271678X231168499 for Zfp580 inactivation as a new therapeutic target to enhance recovery after stroke in mice by Christian J Hoffmann, Melanie TC Kuffner, Leif Koschützke, Stephanie Lorenz, Janet Lips, Philipp Boehm-Sturm, Susanne Mueller, Stefan P Koch, Jeehye An, Lucius S Fekonja, Polina Bugaeva, Andre Rex, Gisela Lättig Tünnemann, Matthias Endres and Christoph Harms in Journal of Cerebral Blood Flow & Metabolism

Ideally, humane endpoints allow for early termination of experiments by minimizing an animal’s discomfort, distress and pain, while ensuring that scientific objectives are reached. Yet, lack of commonly agreed methodology and heterogeneity of cut-off values published in the literature remain a challenge to the accurate determination and application of humane endpoints. With the aim to synthesize and appraise existing humane endpoint definitions for commonly used physiological parameters, we conducted a systematic review of mouse studies of acute and chronic disease models, which used body weight, temperature and/or sickness scores for endpoint definition. In the second part of the study, we used previously published and unpublished data on weight, temperature and sickness scores from mouse models of sepsis and stroke and applied machine learning algorithms to assess the usefulness of this method for parameter selection and endpoint definition across models. Studies were searched for in two electronic databases (MEDLINE/Pubmed and Embase). Out of 110 retrieved full-text manuscripts, 34 studies were included. We found large intra- and inter-model variance in humane endpoint determination and application due to varying animal models, lack of standardized experimental protocols and heterogeneity of performance metrics (part 1). Machine learning models trained with physiological data and sickness severity score or modified DeSimoni neuroscore identified animals with a high risk of death at an early time point in both mouse models of stroke (male: 93.2% at 72h post-treatment; female: 93.0% at 48h post-treatment) and sepsis (96.2% at 24h post-treatment), thus demonstrating generalizability in endpoint determination across models (part 2).

Background Understanding the immune response to combination antiretroviral therapy (cART) is essential for a clear approach to tuberculosis (TB) preventive therapy. We investigated the immunological recovery in cART-treated HIV-infected patients developing TB compared to those who remained free of TB. Methods We extracted data of HIV-infected patients from a multicenter cohort for the HIV clinical surveillance in Germany. No patients included in our study had TB at the beginning of the observation. Using a longitudinal mixed model, we assessed the differences in the mean change of biomarkers (CD4+ cell count, CD8+ cell count, CD4:CD8 ratio and viral load) since cART initiation in patients who remained free of TB vs. those developing TB. To detect the best-fit trajectories of the immunological biomarkers, we applied a multivariable fractional polynomials model. Results We analyzed a total of 10,671 HIV-infected patients including 139 patients who developed TB during follow-up. The highest TB incidences were observed during the first two years since cART initiation (0.32 and 0.50 per 100 person-years). In an adjusted multivariable mixed model, we found that the average change in CD4+ cell count recovery was significantly greater by 33 cells/μl in patients who remained free of TB compared with those developing TB. After the initial three months of cART, 65.6% of patients who remaining free of TB achieved CD4+ count of ≥400 cells/μl, while only 11.3% of patients developing TB reached this immunological status after the three months of cART. We found no differences in the average change of CD8+ cell count, CD4:CD8 ratio or viral load between the two-patient groups. Conclusion All HIV-infected patients responded to cART. However, patients developing TB showed reduced recovery in CD4+ cell count and this might partly explain the incident TB in HIV-infected patients receiving cART. These findings reinforce the importance of adjunctive TB preventive therapy for patients with reduced recovery in CD4+ cell count.

Objective: Current understanding of metastasis formation postulates a multi-step process involving tumor cell intravasation, intravascular circulation, extravasation and intraparenchymal metastasis growth/dormancy. The molecular principles of metastasis formation in the spine remain unknown. The[for full text, please go to the a.m. URL], 65. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC)