Long-term usability and bio-integration of polyimide-based intra-neural stimulating electrodes.

Stimulation of peripheral nerves has transiently restored lost sensation and has the potential to alleviate motor deficits. However, incomplete characterization of the long-term usability and bio-integration of intra-neural implants has restricted their use for clinical applications. Here, we conducted a longitudinal assessment of the selectivity, stability, functionality, and biocompatibility of polyimide-based intra-neural implants that were inserted in the sciatic nerve of twenty-three healthy adult rats for up to six months. We found that the stimulation threshold and impedance of the electrodes increased moderately during the first four weeks after implantation, and then remained stable over the following five months. The time course of these adaptations correlated with the progressive development of a fibrotic capsule around the implants. The selectivity of the electrodes enabled the preferential recruitment of extensor and flexor muscles of the ankle. Despite the foreign body reaction, this selectivity remained stable over time. These functional properties supported the development of control algorithms that modulated the forces produced by ankle extensor and flexor muscles with high precision. The comprehensive characterization of the implant encapsulation revealed hyper-cellularity, increased microvascular density, Wallerian degeneration, and infiltration of macrophages within the endoneurial space early after implantation. Over time, the amount of macrophages markedly decreased, and a layer of multinucleated giant cells surrounded by a capsule of fibrotic tissue developed around the implant, causing an enlargement of the diameter of the nerve. However, the density of nerve fibers above and below the inserted implant remained unaffected. Upon removal of the implant, we did not detect alteration of skilled leg movements and only observed mild tissue reaction. Our study characterized the interplay between the development of foreign body responses and changes in the electrical properties of actively used intra-neural electrodes, highlighting functional stability of polyimide-based implants over more than six months. These results are essential for refining and validating these implants and open a realistic pathway for long-term clinical applications in humans.

[Findings in uteri and ovaries from Eringer cows slaughtered due to fertility problems]. / Befunde von Uterus und Ovarien geschlacbteter Eringerkühe mit Fruchtbarkeitsproblemen.

Eringer cows are often slaughtered due to fertility problems which result from inflammatory and degenerative changes of the uterus or hormonal imbalances. Twenty-one genital tracts from Eringer cows suffering from fertility problems were collected in the abattoir. The purpose of the study was the macroscopic evaluation of the ovaries and the uterus followed by a histological and microbiological analysis of the uterus. Data from inseminations and calvings were provided by the Eringer breeding association and through the internet portal www.agate.ch. Median age of the cows was 6.9 years, number of calves per cow was 2.5 and median period between last calving and slaughter was 1.5 years. In 13 from 21 of the urogenital tracts examined, macroscopic abnormalities of the ovaries and/or histologic or microbiologic findings in the uterus could explain fertility-associated slaughter.

MMTV-like sequences in human breast cancer: a fluorescent PCR/laser microdissection approach.

The hypothesis that a retrovirus homologous to the mouse mammary tumour virus (MMTV) is involved in human breast cancer aetiology has fascinated scientists from many years, but it has never been convincingly demonstrated. Renewed interest in this hypothesis developed when an MMTV env gene-like sequence was found in 38% of human breast cancer tissues. Whereas some subsequent studies confirmed these findings, others did not. The main reasons for this discrepancy, among others, are the different sensitivities and technical details of current molecular approaches to the detection of these sequences. This study is an attempt to find sensitive and reproducible conditions capable of detecting MMTV env-like sequence in human samples. To this end, we first developed a fluorescence nested-PCR (FN-PCR) method that was able to detect very low copies of the viral genome, and then screened a panel of 45 frozen breast cancer samples obtained by laser microdissection. The MMTV env gene-like sequence was found in 15 (33%) of the human breast cancers analysed, whereas the same sequence was detectable neither in normal tissues nor in other types of tumour. Sequence analysis revealed 96% homology with the MMTV genome, but no other significant similarities with the human genome. The combined use of frozen material, microdissected cell populations and FN-PCR provides a novel, sensitive, robust, non-radioactive and fast methodology for the molecular detection of human-MTV. This approach might be successfully used in large molecular studies that aim to investigate the hypothesis of a retroviral aetiology of human breast cancer.