The impact of menopausal status on auditory brainstem responses.

OBJECTIVE: To determine the effect of decreased estrogen levels due to menopause on auditory brainstem response measurements (ABR). STUDY DESIGN: Retrospective chart review. SETTING: Academic. PATIENTS: Pre- and post-menopausal females (pre-M, post-M) and age-matched males. METHODS: ABR measurements of wave I, III, and V latencies, and interpeak latencies; amplitudes of waves I, III, V, and V/I ratio. OUTCOME MEASURE: Differences in ABR measurements between pre-M and post-M. RESULTS: 164 subjects (101 female and 64 male) were included. Post-M had significantly greater latencies (msec) than pre-M of wave V. Post-M had a significantly smaller wave I amplitude (uV) than pre-M. Post-M had a significantly higher wave V/I amplitude ratio than pre-M. Pre-M had significantly shorter latencies than young males for wave III, and wave V. Post-M had significantly shorter latencies than older males at wave III, and wave V. A two-way ANOVA revealed a significant interaction between the effects of age category and gender on V/I amplitude. CONCLUSION: Post-M group showed a significant drop in wave I amplitude compared with pre-M group, even in the absence of hearing loss, suggesting that the gender differences in hearing are related to estrogen signaling along the auditory pathway. If wave I amplitude changes between older and younger groups resulted from decreased peripheral hearing sensitivity, we would expect larger drops in amplitude in males since rates of presbycusis are higher. We observed much larger drops in wave I amplitude in females, which cannot be attributed to peripheral hearing loss. These results may assist in understanding gender differences in presbycusis and a possible protective effect of estrogen on the auditory system. Knowledge of gender differences in wave I may be important when ABR is used to assess possible synaptopathy.

Sex differences in autoimmune inner ear disease treatment and audiological outcomes.

OBJECTIVE: The primary objective of this study was to assess possible sex-related differences in AIED treatment. The secondary aim was to assess the long-term outcomes of treatment using pre- and post-treatment audiometry and speech discrimination scores. METHODS: Adult patients with a diagnosis of AIED who were treated for their condition at the senior author's (RTS) practice from 2010 to 2022 were included in this study. Patients were grouped as males or females for further analysis and comparison. Data included past medical history, medication use, surgical history and social history. Air-conduction thresholds (500 to 8000 Hz) were collected and averaged into discrete variables for pre- and post-treatment. The change (∆) and percent change (%∆) of these variables following therapy were analyzed. Speech discrimination score (SDS) testing results were taken at the same time points as pure tone averages, and patients were sub-stratified based on evidence of improvement in SDS and compared accordingly. RESULTS: One hundred eighty-four patients (78 male/106 female) were included in this study. The mean age of the male participants was 57.18 ± 15.92 years, and the mean age of the female participants was 53.49 ± 16.04 years (p = 0.220). Comorbid autoimmune disease (AD) was more prevalent in females than in males (38.7 % vs. 16.7 %, p = 0.001). Of the patients treated with oral steroids, females received significantly more courses than males (2.554 ± 2.078 vs. 1.946 ± 1.301, p = 0.020). However, the average duration of oral steroids used per trial did not differ significantly between males and females (21.02 ± 18.05 vs. 20.62 ± 7.49, p = 0.135). Audiological results demonstrated that the change (∆) in pure tone average (PTA) at 0.5, 1, 2, and 3 kHz (-4.21 ± 6.394 vs. -3.91 ± 6.105) and high-frequency pure tone average (HFPTA) at 4, 6, and 8 kHz (-4.55 ± 6.544 vs. -2.19 ± 6.842) was not significantly different between the sexes following treatment (p = 0.376 and p = 0.101, respectively). Similarly, the percentage change (%∆) in PTA (-13.17 % vs. -15.01 %) and HFPTA (-8.50 % vs. -6.76 %) also did not differ significantly between males and females (p = 0.900 and p = 0.367, respectively). One hundred-five (57.1 %) patients qualified for the SDS improvement subgroup for analysis, with 50 (47.6 %) being male and 55 (51.9 %) being female (p = 0.159). The change (∆) in SDS (15.12 ± 21.159 vs. 10.62 ± 19.206) and the percentage change (%∆) in SDS (16.71 % vs. 12.40 %) also showed no significant difference between male and female patients (p = 0.312 and p = 0.313, respectively). CONCLUSION: AIED is not a uniform condition regarding clinical presentation, audiological findings or progression, nor is its treatment straightforward. The utilization and duration of cytotoxic medications, as well as PTA and SDS findings, did not differ between the sexes. However, significantly more courses of oral steroids were prescribed to females than males. Sex as a biological variable and its implications in the pathogenesis and treatment of AIED warrant further study.

Identification and characterisation of peptides from a boarfish (Capros aper) protein hydrolysate displaying in vitro dipeptidyl peptidase-IV (DPP-IV) inhibitory and insulinotropic activity.

Twenty-two novel dipeptidyl peptidase-IV (DPP-IV) inhibitory peptides (with IC50 values <200 µM) and fifteen novel insulinotropic peptides were identified in a boarfish protein hydrolysate generated at semi-pilot scale using Alcalase 2.4L and Flavourzyme 500L. This was achieved by bioassay-driven semi-preparative reverse phase-high performance liquid chromatography fractionation, liquid chromatography-mass spectrometry and confirmatory studies with synthetic peptides. The most potent DPP-IV inhibitory peptide (IPVDM) had a DPP-IV half maximal inhibitory concentration (IC50) value of 21.72 ±â€¯1.08 µM in a conventional in vitro and 44.26 ±â€¯0.65 µM in an in situ cell-based (Caco-2) DPP-IV inhibition assay. Furthermore, this peptide stimulated potent insulin secretory activity (1.6-fold increase compared to control) from pancreatic BRIN-BD11 cells grown in culture. The tripeptide IPV exhibited potent DPP-IV inhibitory activity (IC50: 5.61 ±â€¯0.20 µM) comparable to that reported for the known DPP-IV inhibitor IPI (IC50: 3.20 µM). Boarfish proteins contain peptide sequences with potential to play a role in glycaemic management in vivo.

High Density, High Radiance $\mu$ LED Matrix for Optogenetic Retinal Prostheses and Planar Neural Stimulation.

Optical neuron stimulation arrays are important for both in-vitro biology and retinal prosthetic biomedical applications. Hence, in this work, we present an 8100 pixel high radiance photonic stimulator. The chip module vertically combines custom made gallium nitride µ LEDs with a CMOS application specific integrated circuit. This is designed with active pixels to ensure random access and to allow continuous illumination of all required pixels. The µLEDs have been assembled on the chip using a solder ball flip-chip bonding technique which has allowed for reliable and repeatable manufacture. We have evaluated the performance of the matrix by measuring the different factors including the static, dynamic power consumption, the illumination, and the current consumption by each LED. We show that the power consumption is within a range suitable for portable use. Finally, the thermal behavior of the matrix is monitored and the matrix proved to be thermally stable.

Arrays of microLEDs and astrocytes: biological amplifiers to optogenetically modulate neuronal networks reducing light requirement.

In the modern view of synaptic transmission, astrocytes are no longer confined to the role of merely supportive cells. Although they do not generate action potentials, they nonetheless exhibit electrical activity and can influence surrounding neurons through gliotransmitter release. In this work, we explored whether optogenetic activation of glial cells could act as an amplification mechanism to optical neural stimulation via gliotransmission to the neural network. We studied the modulation of gliotransmission by selective photo-activation of channelrhodopsin-2 (ChR2) and by means of a matrix of individually addressable super-bright microLEDs (µLEDs) with an excitation peak at 470 nm. We combined Ca2+ imaging techniques and concurrent patch-clamp electrophysiology to obtain subsequent glia/neural activity. First, we tested the µLEDs efficacy in stimulating ChR2-transfected astrocyte. ChR2-induced astrocytic current did not desensitize overtime, and was linearly increased and prolonged by increasing µLED irradiance in terms of intensity and surface illumination. Subsequently, ChR2 astrocytic stimulation by broad-field LED illumination with the same spectral profile, increased both glial cells and neuronal calcium transient frequency and sEPSCs suggesting that few ChR2-transfected astrocytes were able to excite surrounding not-ChR2-transfected astrocytes and neurons. Finally, by using the µLEDs array to selectively light stimulate ChR2 positive astrocytes we were able to increase the synaptic activity of single neurons surrounding it. In conclusion, ChR2-transfected astrocytes and µLEDs system were shown to be an amplifier of synaptic activity in mixed corticalneuronal and glial cells culture.

A processing platform for optoelectronic/optogenetic retinal prosthesis.

The field of retinal prosthesis has been steadily developing over the last two decades. Despite the many obstacles, clinical trials for electronic approaches are in progress and already demonstrating some success. Optogenetic/optoelectronic retinal prosthesis may prove to have even greater capabilities. Although resolutions are now moving beyond recognition of simple shapes, it will nevertheless be poor compared to normal vision. If we define the aim to be to return mobility and natural scene recognition to the patient, it is important to maximize the useful visual information we attempt to transfer. In this paper, we highlight a method to simplify the scene, perform spatial image compression, and then apply spike coding. We then show the potential for translation on standard consumer processors. The algorithms are applicable to all forms of visual prosthesis, but we particularly focus on optogenetic approaches.

Multi-site optical excitation using ChR2 and micro-LED array.

Studying neuronal processes such as synaptic summation, dendritic physiology and neural network dynamics requires complex spatiotemporal control over neuronal activities. The recent development of neural photosensitization tools, such as channelrhodopsin-2 (ChR2), offers new opportunities for non-invasive, flexible and cell-specific neuronal stimulation. Previously, complex spatiotemporal control of photosensitized neurons has been limited by the lack of appropriate optical devices which can provide 2D stimulation with sufficient irradiance. Here we present a simple and powerful solution that is based on an array of high-power micro light-emitting diodes (micro-LEDs) that can generate arbitrary optical excitation patterns on a neuronal sample with micrometre and millisecond resolution. We first describe the design and fabrication of the system and characterize its capabilities. We then demonstrate its capacity to elicit precise electrophysiological responses in cultured and slice neurons expressing ChR2.

Para-Hisian entrainment: a novel pacing maneuver to differentiate orthodromic atrioventricular reentrant tachycardia from atrioventricular nodal reentrant tachycardia.

INTRODUCTION: Para-Hisian pacing during sinus rhythm can help to identify the presence of an accessory pathway (AP). In this maneuver, the retrograde activation time and pattern are compared during capture and loss-of-capture of the His bundle while pacing from a para-Hisian position. However, identification of a retrograde AP does not necessitate that it is operative during the tachycardia of interest; conversely, slowly conducting or "distant" bypass tracts may not be identified. We evaluated the utility of entrainment or resetting of tachycardias from the para-Hisian position to help distinguish atrioventricular nodal reentrant tachycardia (AVNRT) from orthodromic atrioventricular tachycardia (AVRT). METHODS AND RESULTS: Para-Hisian entrainment/resetting was evaluated in 50 patients: 33 with AVNRT and 17 with AVRT. The maneuvers were performed using a standard quadripolar catheter placed at the His position: low output for right ventricular (RV) capture and high output for both RV and His capture. The retrograde atrial activation sequence, SA interval (interval from stimulus to earliest retrograde atrial activation), and "local" VA interval (interval between the ventricular and atrial electrograms at the site of earliest retrograde atrial activation) were compared between His and His/RV capture. The DeltaSA was > 40 ms in patients with AVNRT and was < 40 ms in all but one patient with AVRT. In concert with the DeltaSA interval, the DeltaVA interval was able to fully define the mechanism of the tachycardia in all patients studied. CONCLUSION: Para-Hisian entrainment/resetting can determine the course of retrograde conduction operative during narrow complex tachycardias. It is a useful diagnostic maneuver in differentiating AVNRT and orthodromic AVRT.

Variability in implantable cardioverter defibrillator pulse generator longevity between manufacturers.

ICDs are used frequently to treat malignant ventricular arrhythmias. Despite the expanding role of these devices, little is known about the manufacturer variability in the performance of ICD generators. The purpose of this study is to explore the indications for ICD pulse generator replacement and to examine performance differences between the three major manufacturers of ICDs in the United States. The authors performed a retrospective review of ICD pulse generators that were implanted and replaced at Massachusetts General Hospital between February 1998 and March 2002. During the study period, 50 (7%) of the 707 devices in the study cohort were replaced. The most common indication for pulse generator replacement was related to battery performance followed by device recall, upgrade to a dual chamber device, and pulse generator malfunction. After exclusion of the recalled devices, a significantly higher number of pulse generators manufactured by St. Jude Medical (14/229) required replacement for battery depletion or prolonged change times during the study period compared with devices from Guidant (2/220) or Medtronic (0/273), P = 0.003 and P < 0.0001, respectively. This difference was attributable to reduced longevity in the Angstrom series of defibrillators.

Surgical coronary revascularization and antiarrhythmic therapy in survivors of out-of-hospital cardiac arrest.

BACKGROUND: Patients who survive out-of-hospital cardiac arrest are at high risk for recurrent arrest. Coronary artery bypass grafting (CABG) confers a survival advantage, but it is unclear whether antiarrhythmic drugs or an implanted defibrillator confer added benefit. This study was designed to determine predictors for further treatment, survival, and therapeutic internal cardiac defibrillator (ICD) discharge in this patient population. METHODS: One hundred and eight patients undergoing CABG after out-of-hospital cardiac arrest were identified over a 12-year period. Case records were retrospectively reviewed. Follow-up was obtained and predictors of outcome events were analyzed. RESULTS: Fifty-four (50%) patients underwent CABG only. Fifty-four received additional treatment that included ICD placement in 23 (21%), antiarrhythmic medications in 19 (18%), or both in 12 (11%). Predictors of ICD placement included left ventricular ejection fraction (LVEF) less than 40% and perioperative intraaortic balloon counterpulsation. ICD or medical management increased survival in patients with LVEF <40%. Predictors of increased mortality included age >65 years, Cleveland Severity Score >8, and female gender. Predictors of therapeutic ICD discharge included age >65 years, reoperative CABG, LVEF <40%, and positive postoperative electrophysiological (EP) study. No patient with a negative postoperative EP study received an ICD, and none suffered sudden cardiac death during follow-up. CONCLUSIONS: Patients with coronary artery disease anatomically suitable for CABG who survive an acute out-of-hospital cardiac arrest should undergo EP testing after CABG. Approximately half of these patients are adequately treated by CABG alone. The remainder may benefit from ICD placement or medical antiarrhythmic management.

Magnesium deficiency during lactation as a precipitant of ventricular tachyarrhythmias.

A young ICD recipient with a history of syncope and idiopathic polymorphic ventricular tachycardia/ventricular fibrillation presented after an ICD discharge. She had delivered her first child 8 days prior to the event and she had been lactating. Numerous short runs of polymorphic ventricular tachycardia/ventricular fibrillation resolved with aggressive replacement of magnesium and elimination of breast-feeding.