Expression of Connexins 37, 43 and 45 in Developing Human Spinal Cord and Ganglia.

Direct intercellular communication via gap junctions has an important role in the development of the nervous system, ranging from cell migration and neuronal differentiation to the formation of neuronal activity patterns. This study characterized and compared the specific spatio-temporal expression patterns of connexins (Cxs) 37, 43 and 45 during early human developmental stages (since the 5th until the 10th developmental week) in the spinal cord (SC) and dorsal root ganglia (DRG) using double immunofluorescence and transmission electron microscopy. We found the expression of all three investigated Cxs during early human development in all the areas of interest, in the SC, DRG, developing paravertebral ganglia of the sympathetic trunk, notochord and all three meningeal layers, with predominant expression of Cx37. Comparing the expression of different Cxs between distinct developmental periods, we did not find significant differences. Specific spatio-temporal pattern of Cxs expression might reflect their relevance in the development of all areas of interest via cellular interconnectivity and synchronization during the late embryonic and early fetal period of human development.

[Barriers and facilitators for the development of sex/gender sensitive clinical practice guidelines: A qualitative interview study]. / Barrieren und Förderfaktoren für die Entwicklung von geschlechtersensiblen medizinischen Leitlinien ­ Eine qualitative Befragung.

INTRODUCTION: Sex and gender health research evaluates biological and psychosocial differences between women and men which can influence the development, progress and experience of diseases. However, despite the increasing body of evidence about relevant differences between women and men regarding healthcare, the prevention, management and treatment of many common diseases do not yet reflect the knowledge of sex/gender characteristics. Furthermore, in the development of clinical practice guidelines, which are a valuable tool for knowledge transfer between scientific evidence and healthcare, sex/gender factors are only rarely explicitly and systematically considered. The goal of the current study therefore is to identify barriers and facilitators for the consideration and integration of sex/gender differences into guidelines, to create a basis for potential solutions and tools to increase the development of sex/gender sensitive guidelines in the future. METHODS: Barriers and facilitators for the development of sex/gender sensitive guidelines were identified by conducting semi-structured interviews with twelve experts in national and international guideline development (guideline authors and coordinators), as well as gender experts (female: n=8). The selection of experts followed a purposeful sampling strategy and the interview data was analyzed using the qualitative content analysis according to Mayring. RESULTS: The views on barriers and facilitators were allocated to and summarized in five categories with ten subcategories. The identified barriers mainly addressed the increasing complexity of guidelines, the lack of availability and quality of sex/gender sensitive evidence, and the shortage of resources. In addition, barriers were identified in an individual/professional context, such as deficiencies in awareness/knowledge about relevant sex/gender differences. The results of facilitating factors showed that experts see political policies and standards from guideline organizations as support for the consideration of sex/gender factors in guideline development. CONCLUSION: The perspective of experts illustrates that besides organizational and political inventions, individual and social factors should also be addressed in order to achieve behavioral change.

Disrupted TH17/Treg balance in patients with chronic low back pain.

UNLABELLED: Chronic low back pain (CLBP) is a leading cause of disability and costs in health care systems worldwide. Despite extensive research, the exact pathogenesis of CLBP, particularly the individual risk of chronification remains unclear. To investigate a possible role of the adaptive immune system in the pathophysiology of CLBP, we analyzed T cell related cytokine profiles, T cell related mRNA expression patterns and the distribution of T cell subsets in 37 patients suffering from nonspecific CLBP before and after multimodal therapy in comparison to 25 healthy controls. Serum patterns of marker cytokines were analyzed by Luminex technology, mRNA expression of cytokines and specific transcription factors was measured by real-time PCR, and distribution of TH1-, TH2-, TH17- and regulatory T cell (Tregs) subsets was determined by multicolor flow cytometry. We found that CLBP patients exhibit an increased number of anti-inflammatory Tregs, while pro-inflammatory TH17 cells are decreased, resulting in an altered TH17/Treg ratio. Accordingly, FoxP3 and TGF-ß-mRNA expression was elevated, while expression of IL-23 was reduced. Serum cytokine analyses proved to be unsuitable to monitor the adaptive immune response in CLBP patients. We further show that even after successful therapy with lasting reduction of pain, T cell subset patterns remained altered after a follow-up period of 6 months. These findings suggest an involvement of TH17/Treg cells in the pathogenesis of CLBP and emphasize the importance of these cells in the crosstalk of pain and immune response. TRIAL REGISTRATION: German Clinical Trial Register: Registration Trial DRKS00005954.