Schwann Cell Metabolic Activity in Various Short-Term Holding Conditions: Implications for Improved Nerve Graft Viability

Strategies for improvement of nerve regeneration and optimal conditions to prevent Schwann cell (SC) loss within a nerve transplant procedure are critical. The purpose of this study was to examine SC viability, which plays an important role in peripheral nerve regeneration, under various incubation conditions up to three hours. To address this issue, Schwann cell metabolic activity was determined using different independent test methods. The following experimental conditions were compared: SCs prepared from nerves were incubated in (1) isotonic saline solution (2) Dulbecco's modified Eagles medium as used for cell culturing, (3) Hannover bioreactor medium, and (4) Leibovitz's medium. SC metabolic activity of excised rat sciatic nerve was determined at 4°C, 18°C, and 37°C over 3 hrs. The results indicate that SC activity was optimized by the usage of Leibovitz's medium or HBRM at 37°C. Greater SC viability at the time of surgical nerve grafting could contribute to improved axonal regeneration and remyelination after nerve transplantation, and thus more successful functional recovery

Charité Caesarean Birth Improves Birth Experience in Planned and Unplanned Caesarean Sections While Maintaining Maternal and Neonatal Safety: A Prospective Cohort Study

Background: In this study, we aimed to assess the safety of a modified caesarean delivery (Charite caesarean birth) in an extended frame of indications, and to examine its impact on parents' birth experience and long-term effects. Methods: This prospective cohort study was performed from January to June 2019. A standardized questionnaire was given to all women who gave birth as an inpatient delivery. Eight months after hospital discharge, all women who gave consent were sent a follow-up questionnaire including questions on current feelings, breast feeding, bonding, and support system, as well as a screening for postnatal depression. Indications for caesarean delivery included preterm birth, fetal malpresentation, fetal malformation, twin pregnancy, and maternal pre-existing conditions. Results: The study cohort included 110 women. The mode of delivery was spontaneous in 49%, per vacuum extraction in 15%, conventional caesarean section in 7%, and Charite caesarean birth in 29%. The groups with Charite versus conventional caesarean delivery did not significantly differ in neonatal admission rates, umbilical cord parameters, maternal blood loss, or duration of surgery. Compared to conventional caesarean delivery, women who underwent a Charite caesarean delivery were significantly more satisfied with their birth experience. At follow-up, the mode of delivery was not associated with significant differences in postnatal depression, breast feeding, or bonding parameters. Conclusions: Outside of emergency situations, Charite caesarean birth improves patients' well-being, without increased maternal and neonatal morbidity

Femtosecond laser generation of bimetallic oxide nanoparticles with potential X-ray absorbing and magnetic functionalities for medical imaging applications

Bimetallic nanoparticles have gained vivid attention due to their unique and synergistic properties. They can be used in fields such as solar cells, optics, sensing, as well as medicine. The generation of bimetallic nanoparticles, containing oxide phases of both magnetic and X-ray attenuating metals for bioimaging applications has been challenging with traditional chemical synthesis methods. An alternative is the generation of nanoparticles from binary oxide ceramics by laser ablation in liquid. However, the applicability of this technique for production of hybrid nanoparticles consisting of magnetic and X-ray absorbing elements has not been demonstrated yet. In this work, novel ceramics composed of bimetallic oxide phases of iron-tantalum, iron-tungsten, and ironbismuth were produced by a reaction-sintering method. The bulk samples were characterized with scanning electron microscopy, energy dispersive X-ray spectroscopy, and X-ray diffractometry. Nanoparticles were produced in aqueous and ethanol solutions by employing a femtosecond laser and characterized with transmission electron microscopy, selected area electron diffraction, and energy dispersive X-ray spectroscopy. The results demonstrated that the production of binary oxide bulk ceramics and their subsequent laser ablation in liquids leads to the successful generation of bimetallic oxide nanoparticles, without a core-shell morphology. In addition, it was found that the ablation threshold fluence of bulk samples as well as the crystallinity of the synthesized nanoparticles is governed by both the nature of the metallic oxide ceramics and the employed liquid. The results pave the way for a single step generation of well-defined bimetallic nanoparticles by laser ablation that could potentially exhibit X-ray and magnetic absorption properties suitable for multimodal imaging applications.This research has been partially funded by the Spanish Ministerio de Ciencia e Innovacion through the research project MAT2015-67354R (MINECO-FEDER). Funding through a Marie Sklodowska-Curie Individual Fellowships (MSCA-IF 2014, 656908-NIMBLIS-ESR) of the Horizon 2020 program, and the Project PI-0030-2017 of the Junta de Andalucia in the framework of the integrated territorial initiative 20142020 for research and innovation in biomedicine and health sciences in the province of Cadiz is also greatly appreciated. The authors acknowledge support for scanning electron microscopy by Dr. Stephan Puchegger and the faculty center for nanostructure research at the University of Vienna

Intentional and unintentional medication nonadherence in psoriasis: the role of patients’ medication beliefs and habit strength [abstract only]

The accurate diagnosis of psoriasis has remained a challenge, as no disease-specific biomarkers have yet been identified. Currently, the diagnosis of chronic inflammatory diseases relies mainly on the assessment of visible symptoms or the histological features of the biopsy. This approach is heavily reliant on the experience of the clinician and, therefore, may lead to misdiagnosis as there are numerous different chronic inflammatory skin diseases that may present similar clinical features. Hence, the need for diagnostic biomarkers is clear. Although different investigations have reported the discovery of potential psoriasis biomarkers, still no accurate and reliable biomarker is available. Rather than searching for a single valid biomarker, we propose that applying a multicomponent bio-marker-based approach would result in a higher degree of success and translation into clinical practice. An extensive review of published studies to identify the most relevant psoriasis-specific biomarker candidates was conducted. This led us to conclude that the expression levels of specific genes in the skin hold the most promise as discriminatory biomarkers, resulting in the selection of five genes, the expression levels of which have been demonstrated to be exclusive for psoriasis vulgaris. We first conducted a preliminary validation study applying support vector machine-based classification and principle component analysis on the skin-derived expression data of 12 patients with psoriasis vulgaris and 12 healthy controls, previously produced in our departments. We then confirmed that the expression levels of the five genes in psoriatic lesions indeed present a unique pattern. Encouraged by these results, we continued to develop a quantitative polymerase chain reaction panel to allow the accurate measurement of expression levels for the five genes to be used in the studies to follow. Although we have yet to confirm these results in the context of other chronic inflammatory skin diseases, the results of previously published studies regarding these five genes are promising. Therefore, we are in the process of collecting additional skin samples from patients with chronic inflammatory disease (including different papulosquamous disorders and atopic dermatitis) to validate the discriminatory power of our panel. These results may further be translated to viable clinical diagnostic tests in the near future. This work was supported by the ERA Chair for Translational Genomics and Personalized Medicine at the University of Tartu

Schwann cell stimulation induces functional and structural changes in peripheral nerves

Signal propagation is the essential function of nerves. Lysophosphatidic acid 18:1 (LPA) allows the selective stimulation of calcium signaling in Schwann cells but not neurons. Here, the time course of slowing and amplitude reduction on compound action potentials due to LPA exposure was observed in myelinated and unmyelinated fibers of the mouse, indicating a clear change of axonal function. Teased nerve fiber imaging showed that Schwann cell activation is also present in axon-attached Schwann cells in freshly isolated peripheral rat nerves. The LPA receptor 1 was primarily localized at the cell extensions in isolated rat Schwann cells, suggesting a role in cell migration. Structural investigation of rat C-fibers demonstrated that LPA leads to an evagination of the axons from their Schwann cells. In A-fibers, the nodes of Ranvier appeared unchanged, but the Schmidt-Lanterman incisures were shortened and myelination reduced. The latter might increase leak current, reducing the potential spread to the next node of Ranvier and explain the changes in conduction velocity. The observed structural changes provide a plausible explanation for the functional changes in myelinated and unmyelinated axons of peripheral nerves and the reported sensory sensations such as itch and pain

Spider Silk Constructs Enhance Axonal Regeneration and Remyelination in Long Nerve Defects in Sheep

BACKGROUND: Surgical reapposition of peripheral nerve results in some axonal regeneration and functional recovery, but the clinical outcome in long distance nerve defects is disappointing and research continues to utilize further interventional approaches to optimize functional recovery. We describe the use of nerve constructs consisting of decellularized vein grafts filled with spider silk fibers as a guiding material to bridge a 6.0 cm tibial nerve defect in adult sheep. METHODOLOGY/PRINCIPAL FINDINGS: The nerve constructs were compared to autologous nerve grafts. Regeneration was evaluated for clinical, electrophysiological and histological outcome. Electrophysiological recordings were obtained at 6 months and 10 months post surgery in each group. Ten months later, the nerves were removed and prepared for immunostaining, electrophysiological and electron microscopy. Immunostaining for sodium channel (NaV 1.6) was used to define nodes of Ranvier on regenerated axons in combination with anti-S100 and neurofilament. Anti-S100 was used to identify Schwann cells. Axons regenerated through the constructs and were myelinated indicating migration of Schwann cells into the constructs. Nodes of Ranvier between myelin segments were observed and identified by intense sodium channel (NaV 1.6) staining on the regenerated axons. There was no significant difference in electrophysiological results between control autologous experimental and construct implantation indicating that our construct are an effective alternative to autologous nerve transplantation. CONCLUSIONS/SIGNIFICANCE: This study demonstrates that spider silk enhances Schwann cell migration, axonal regrowth and remyelination including electrophysiological recovery in a long-distance peripheral nerve gap model resulting in functional recovery. This improvement in nerve regeneration could have significant clinical implications for reconstructive nerve surgery

HES1 in immunity and cancer

Hairy and enhancer of split homolog-1 (HES1) is a part of an extensive family of basic helix-loop-helix (bHLH) proteins and plays a crucial role in the control and regulation of cell cycle, proliferation, cell differentiation, survival and apoptosis in neuronal, endocrine, T-lymphocyte progenitors as well as various cancers. HES1 is a transcription factor which is regulated by the NOTCH, Hedgehog and Wnt signalling pathways. Aberrant expression of these pathways is a common feature of cancerous cells. There appears to be a fine and complicated crosstalk at the molecular level between the various signalling pathways and HES1, which contributes to its effects on the immune response and cancers such as leukaemia. Several mechanisms have been proposed, including an enhanced invasiveness and metastasis by inducing epithelial mesenchymal transition (EMT), in addition to its strict requirement for tumour cell survival. In this review, we summarize the current biology and molecular mechanisms as well as its use as a clinical target in cancer therapeutics

Effect of albumin substitution on pharmacokinetics of piperacillin/tazobactam in patients with severe burn injury admitted to the ICU

Background: Pathophysiological changes in severely burned patients alter the pharmacokinetics (PK) of anti-infective agents, potentially leading to subtherapeutic concentrations at the target site. Albumin supplementation, to support fluid resuscitation, may affect pharmacokinetic properties by binding drugs. This study aimed to investigate the PK of piperacillin/tazobactam in burn patients admitted to the ICU before and after albumin substitution as total and unbound concentrations in plasma. Patients and methods: Patients admitted to the ICU and scheduled for 4.5 g piperacillin/tazobactam administration and 200 mL of 20% albumin substitution as part of clinical routine were included. Patients underwent IV microdialysis, and simultaneous arterial plasma sampling, at baseline and multiple timepoints after drug administration. PK analysis of total and unbound drug concentrations under steady-state conditions was performed before and after albumin supplementation. Results: A total of seven patients with second- to third-degree burns involving 20%-60% of the total body surface were enrolled. Mean (SD) AUC0-8 (h·mg/L) of total piperacillin/tazobactam before and after albumin substitution were 402.1 (242)/53.2 (27) and 521.8 (363)/59.7 (32), respectively. Unbound mean AUC0-8 before and after albumin supplementation were 398.9 (204)/54.5 (25) and 456.4 (439)/64.5 (82), respectively. Conclusions: Albumin supplementation had little impact on the PK of piperacillin/tazobactam. After albumin supplementation, there was a numerical increase in mean AUC0-8 of total and unbound piperacillin/tazobactam, whereas similar Cmax values were observed. Future studies may investigate the effect of albumin supplementation on drugs with a higher plasma protein binding