Psychosocial impact of undergoing prostate cancer screening for men with BRCA1 or BRCA2 mutations.

OBJECTIVES: To report the baseline results of a longitudinal psychosocial study that forms part of the IMPACT study, a multi-national investigation of targeted prostate cancer (PCa) screening among men with a known pathogenic germline mutation in the BRCA1 or BRCA2 genes. PARTICPANTS AND METHODS: Men enrolled in the IMPACT study were invited to complete a questionnaire at collaborating sites prior to each annual screening visit. The questionnaire included sociodemographic characteristics and the following measures: the Hospital Anxiety and Depression Scale (HADS), Impact of Event Scale (IES), 36-item short-form health survey (SF-36), Memorial Anxiety Scale for Prostate Cancer, Cancer Worry Scale-Revised, risk perception and knowledge. The results of the baseline questionnaire are presented. RESULTS: A total of 432 men completed questionnaires: 98 and 160 had mutations in BRCA1 and BRCA2 genes, respectively, and 174 were controls (familial mutation negative). Participants' perception of PCa risk was influenced by genetic status. Knowledge levels were high and unrelated to genetic status. Mean scores for the HADS and SF-36 were within reported general population norms and mean IES scores were within normal range. IES mean intrusion and avoidance scores were significantly higher in BRCA1/BRCA2 carriers than in controls and were higher in men with increased PCa risk perception. At the multivariate level, risk perception contributed more significantly to variance in IES scores than genetic status. CONCLUSION: This is the first study to report the psychosocial profile of men with BRCA1/BRCA2 mutations undergoing PCa screening. No clinically concerning levels of general or cancer-specific distress or poor quality of life were detected in the cohort as a whole. A small subset of participants reported higher levels of distress, suggesting the need for healthcare professionals offering PCa screening to identify these risk factors and offer additional information and support to men seeking PCa screening

A gated differential amplifier for recording physiological responses to electrical stimulation

Publisher’s permission requested and denied.Artifact from electrical stimulation imposes a problem for the recording of physiological responses to electrical stimulation. Here we describe a simple, low-cost, gated differential amplifier for the recording of physiological responses to electrical stimulation. The gain of the amplifier is set to 1 during electrical stimulation by setting the gate input to a high logic state to avoid overloading of the amplifier by the artifact. Following electrical stimulation, the gate input is set to a low logic state, resulting in again of 1000 for frequencies between 300 Hz and 25 kHz ( -3 dB points). The gain at low frequencies (0-0.2 Hz) is held constant at 1 to avoid transients in the output signal arising from changes in gain at these frequencies. The gain of the amplifier following stimulation (gate low) was independent of the magnitude of the artifact and was therefore suitable for the measurement of neural field potentials with low impedance electrodes

Chronic electrical stimulation of the auditory nerve at high stimulus rates: a physiological and histopathological study

Publisher’s permission requested and denied.A major factor associated with recent improvements in the clinical performance of cochlear implant patients has been the development of speech-processing strategies based on high stimulation rates. While these processing strategies show clear clinical advantage, we know little of their long-term safety implications. The present study was designed to evaluate the physiological and histopathological effects of long-term intracochlear electrical stimulation using these high rates. Thirteen normal-hearing adult cats were bilaterally implanted with scala tympani electrode arrays and unilaterally stimulated for periods of up to 2100 h using either two pairs of bipolar or three monopolar stimulating electrodes. Stimuli consisted of short duration (25-50 µs/phase) charge-balanced biphasic current pulses presented at 1000 pulses per second (pps) per channel for monopolar stimulation, and 2000 pps/channel for bipolar stimulation. The electrodes were shorted between current pulses to minimize any residual direct current, and the pulse trains were presented using a 50% duty cycle (500 ms on; 500 ms oft) in order to simulate speech. Both acoustic (ABR) and electrical (EABR) auditory brainstem responses were recorded periodically during the chronic stimulation program, All cochleas showed an increase in the click-evoked ABR threshold following implant surgery; however, recovery to near-normal levels occurred in approximately half of the stimulated cochleas 1 month post-operatively. The use of frequency-specific stimuli indicated that the most extensive hearing loss generally occurred in the high-frequency basal region of the cochlea (12 and 24 kHz) adjacent to the stimulating electrode. However, thresholds at lower frequencies (2, 4 and 8 kHz), appeared at near-normal levels despite long-term electrode implantation and electrical stimulation. Our longitudinal EABR results showed a statistically significant increase in threshold in nearly 40% of the chronically stimulated electrodes evaluated; however, the gradient of the EABR input/output (I/O) function (evoked potential response amplitude versus stimulus current) generally remained quite stable throughout the chronic stimulation period. Histopathological examination of the cochleas showed no statistically significant difference in ganglion cell densities between cochleas using monopolar and bipolar electrode configurations (P = 0.67), and no evidence of cochlear damage caused by high-rate electrical stimulation when compared with control cochleas. Indeed, there was no statistically significant relationship between spiral ganglion cell density and electrical stimulation (P = 0.459), or between the extent of loss of inner (IHC, P = 0.86) or outer (OHC, P=0.30) hair cells and electrical stimulation. Spiral ganglion cell loss was, however, influenced by the degree of inflammation (P=0.016) and electrode insertion trauma. These histopathological findings were consistent with the physiological data. Finally, electrode impedance, measured at completion of the chronic stimulation program, showed close correlation with the degree of tissue response adjacent to the electrode array. These results indicated that chronic intracochlear electrical stimulation, using carefully controlled charge-balanced biphasic current pulses at stimulus rates of up to 2000 pps/channel, does not appear to adversely affect residual auditory nerve elements or the cochlea in general. This study provides an important basis for the safe application of improved speech-processing strategies based on high-rate electrical stimulation

High rate electrical stimulation of the auditory nerve: physiological and pathological results [Abstract]

Previous experimental studies have shown that chronic electrical stimulation of the auditory nerve using charge balanced biphasic current pulses at rates of up to 500 pulses per second (pps) do not adversely affect the adjacent spiral ganglion population. More recently, a number of clinical trials have indicated that speech processing strategies based on high pulse rates (1000 pps and more), can further improve speech perception. In this paper we summarize our results following acute and chronic electrical stimulation of the auditory nerve using high pulse rates.19-24 Augus

Potential applications of a small and high surface area platinum electrode as an implanted impedance bio-sensor or recording electrode.

A small Platinum (Pt) electrode (geometric area: -0.43 mm2) was treated in an electrochemical etching process, to produce a highly porous columnar thin layer (-600 nm) on the surface of the electrode. The modified Pt electrode (Pt-p) showed similar electrical properties to a platinum-black electrode but with high mechanical integrity. Previous studies of chronic stimulation had also shown good biocompatibility and surface stability over several months implantation. This paper discusses the potential applications of the modified electrode as an implanted bio-sensor: (1) as a recording electrode compared to an untreated Pt electrode. (2) as a probe in detecting electrical characteristics of living biological material adjacent to the electrode in vivo, which may correlate to inflammation or trauma repair. Results of electrochemical impedance spectroscopy (BIS) revealed much lower electrode interface polarisation impedance, reduced overall electrode impedance, and a largely constant impedance above 100 Hz for the Pt-p electrode compared with untreated Pt electrodes. This provides a platform for recording biological events with low noise interference. Results of A.C. impedance spectroscopy of the high surface area electrode only reflect changes in the surrounding biological environment in the frequency range (1 kHz to 100kHz), interference from electrode polarisation impedance can be neglected. The results imply that the surface-modified electrode is a good candidate for application to implantable biosensors for detecting bio-electric events. The modification procedure and its high surface area concept could have application to a smart MEMS device or microelectrode.13-15 Decembe

Promoting neurite outgrowth from spiral ganglion neuron explants using polypyrrole/BDNF-coated electrodes

Release of neurotrophin-3 (NT3) and brain-derived neurotrophic factor (BDNF) from hair cells in the cochlea is essential for the survival of spiral ganglion neurons (SGNs). Loss of hair cells associated with a sensorineural hearing loss therefore results in degeneration of SGNs, potentially reducing the performance of a cochlear implant. Exogenous replacement of either or both neurotrophins protects SGNs from degeneration after deafness. We previously incorporated NT3 into the conducting polymer polypyrrole (Ppy) synthesized with para-toluene sulfonate (pTS) to investigate whether Ppy/pTS/NT3-coated cochlear implant electrodes could provide both neurotrophic support and electrical stimulation for SGNs. Enhanced and controlled release of NT3 was achieved when Ppy/pTS/NT3-coated electrodes were subjected to electrical stimulation. Here we describe the release dynamics and biological properties of Ppy/pTS with incorporated BDNF. Release studies demonstrated slow passive diffusion of BDNF from Ppy/pTS/BDNF, with electrical stimulation significantly enhancing BDNF release over 7 days. A 3-day SGN explant assay found that neurite outgrowth from explants was 12.3-fold greater when polymers contained BDNF (p \u3c 0.001), although electrical stimulation did not increase neurite outgrowth further. The versatility of Ppy to store and release neurotrophins, conduct electrical charge, and act as a substrate for nerve-electrode interactions is discussed for specialized applications such as cochlear implants

Electrical Stimulation Promotes Cardiac Differentiation of Human Induced Pluripotent Stem Cells

Background. Human induced pluripotent stem cells (iPSCs) are an attractive source of cardiomyocytes for cardiac repair and regeneration. In this study, we aim to determine whether acute electrical stimulation of human iPSCs can promote their differentiation to cardiomyocytes. Methods. Human iPSCs were differentiated to cardiac cells by forming embryoid bodies (EBs) for 5 days. EBs were then subjected to brief electrical stimulation and plated down for 14 days. Results. In iPS(Foreskin)-2 cell line, brief electrical stimulation at 65 mV/mm or 200 mV/mm for 5 min significantly increased the percentage of beating EBs present by day 14 after plating. Acute electrical stimulation also significantly increased the cardiac gene expression of ACTC1, TNNT2, MYH7, and MYL7. However, the cardiogenic effect of electrical stimulation was not reproducible in another iPS cell line, CERA007c6. Beating EBs from control and electrically stimulated groups expressed various cardiac-specific transcription factors and contractile muscle markers. Beating EBs were also shown to cycle calcium and were responsive to the chronotropic agents, isoproterenol and carbamylcholine, in a concentration-dependent manner. Conclusions. Our results demonstrate that brief electrical stimulation can promote cardiac differentiation of human iPS cells. The cardiogenic effect of brief electrical stimulation is dependent on the cell line used

Preclinical safety study of a fully implantable, sub-scalp ring electrode array for long-term EEG recordings

Objective. Long-term electroencephalogram (EEG) recordings can aid diagnosis and management of various neurological conditions such as epilepsy. In this study we characterize the safety and stability of a clinical grade ring electrode arrays by analyzing EEG recordings, fluoroscopy, and computed tomography (CT) imaging with long-term implantation and histopathological tissue response. Approach. Seven animals were chronically implanted with EEG recording array consisting of four electrode contacts. Recordings were made bilaterally using a bipolar longitudinal montage. The array was connected to a fully implantable micro-processor controlled electronic device with two low-noise differential amplifiers and a transmitter-receiver coil. An external wearable was used to power, communicate with the implant via an inductive coil, and store the data. The sub-scalp electrode arrays were made using medical grade silicone and platinum. The electrode arrays were tunneled in the subgaleal cleavage plane between the periosteum and the overlying dermis. These were implanted for 3-7 months before euthanasia and histopathological assessment. EEG and impedance were recorded throughout the study. Main results. Impedance measurements remained low throughout the study for 11 of 12 channels over the recording period ranged from 3 to 5 months. There was also a steady amplitude of slow-wave EEG and chewing artifact (noise). The post-mortem CT and histopathology showed the electrodes remained in the subgaleal plane in 6 of 7 sheep. There was minimal inflammation with a thin fibrotic capsule that ranged from 4 to 101 μm. There was a variable fibrosis in the subgaleal plane extending from 210 to 3617 μm (S3-S7) due to surgical cleavage. One sheep had an inflammatory reaction due to electrode extrusion. The passive electrode array extraction force was around 1 N. Significance. Results show sub-scalp electrode placement was safe and stable for long term implantation. This is advantageous for diagnosis and management of neurological conditions where long-term, EEG monitoring is required.</p