Multifaceted understanding of human nerve implants to design optimized electrodes for bioelectronics.

Bioelectronic medicine is a promising venue for treatment of disabilities using implantable neural interfaces. Peripheral neurostimulation of residual nerves recently enabled multiple functional benefits in amputees. Despite the preliminary promising impact on patients' life, the over-time stability of implants and the related nerve reactions are unclear. To unveil the mechanisms and inform the design of better nerve-electrode interfaces, we engaged a multifaceted approach, merging functional responses from patients, their histological data, and corresponding computational modelling. Neurostimulation evoked different selective sensation locations and qualities over-time, with respective perceptual thresholds, that showed different degree of time stabilities dependent from the stimulating active sites. The histological analysis after explant showed mild tissue reactions, while electromechanically active sites and substrates remained conserved. Computational models, based on patients' histology, revealed the direct influence of the simulated tissue reaction to change of thresholds and type of perceived sensations. Novel insights of electrode biocompatibility was observed compared to animals and the increase of thresholds could be predicted computationally. This multifaced framework suggest that future intraneural implants should have easier implantation and higher biocompatibility counteracting the sensations changes through AI-based stimulations and electrode coatings.

The expression of Ki-67 and Bcl-2 in Hodgkin's lymphoma: correlation with the International Prognostic Score and bulky disease: a study by the Serbian Lymphoma Study Group (SLG).

The prognosis of Hodgkin's lymphoma has been improved over last 10 yr due to identification of prognostic parameters. These factors may predict the clinical outcome and therefore may have influence on the selection of appropriate treatment. In a cohort of 40 patients with Hodgkin's lymphoma of nodular sclerosis subtype, treated with ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) regimen, we analyzed prognostic relevance of the expression of Ki-67 and Bcl-2 at diagnosis as well as other clinical parameters: International Prognostic Score, bulky disease, tissue eosinophilia, and high erythrocyte sedimentation rate. Significance was tested according to response rate and overall survival. Patients with a high proliferative fraction (Ki-67 > 50%) had worse overall survival compared with those with low proliferation, 56% vs 91%. There was a correlation between Ki-67 positivity and the achievement of complete remission. Cox's multivariate model revealed that Ki-67 positivity at threshold of 50% was a significant independent prognostic factor. The Bcl-2 expression in less than 50% of tumor cells was detected in 65.5% of patients, and in a majority of cases it was associated with complete remission. Patients with high IPS had more progressive disease and shorter survival. Bulky disease, tissue eosinophilia, and high erythrocyte sedimentation rate had no significant influence on complete remission and survival. However, there was a marked divergence in survival curves after 4 yr follow-up for each of these parameters. Patients with high Ki-67, IPS > 3, bulky disease, tissue eosinophilia, and high sedimentation rate are at a higher risk of treatment failure and relapse and therefore might be eligible for other aggressive therapeutic approach.

Glutathione S-transferase-P1 expression correlates with increased antioxidant capacity in transitional cell carcinoma of the urinary bladder.

OBJECTIVES: Our aim was to perform a comprehensive analysis of the antioxidant capacity of transitional cell carcinoma (TCC) of urinary bladder and discern the role of enzymes associated with glutathione (GSH) in maintaining high GSH levels in these tumours. Because the redox-sensitive protein glutathione S-transferase P1 (GSTP1) might provide an important link between high antioxidant capacity and inhibition of apoptotic pathways, we also explored how the redox state in tumour cells interacts with the expression of GSTP1. METHODS: We examined spectrophotometrically the specific activities of GSH-replenishing enzymes involved in GSH synthesis (gamma-glutamylcysteine synthetase, gamma-GCS), GSH regeneration (glutathione reductase, GR), and antioxidant protection (glutathione peroxidase, GPX; superoxide dismutase, SOD) in the cytosolic fraction of tumours and the surrounding normal tissue of 30 TCC patients. GSTP1-1 expression was also analyzed. RESULTS: We found a significant increase in the activity of both GSH-replenishing and antioxidant enzymes as well as enhanced GSTP1-1 expression in tumours in comparison with adjacent normal uroepithelium. Mean gamma-GCS and GR activities in tumours were about 4- and 2-fold higher, respectively, than in corresponding normal tissue. Expression of GSTP1 correlated significantly with GSH level and gamma-GCS and GR activities. GPX and SOD activities in TCC were also markedly increased. CONCLUSIONS: Enhanced GSH-replenishing pathways account for increased GSH levels in TCC. Upregulated GPX and SOD also contribute to high antioxidant potential in TCC. Under such conditions, expression of redox-sensitive GSTP1 protein is upregulated.