CO2-formatics: how do proteins bind carbon dioxide?

The rising atmospheric concentration of CO(2) has motivated researchers to seek routes for improved utilization, increased mitigation, and enhanced sequestration of this greenhouse gas. Through a combination of bioinformatics, molecular modeling, and first-principles quantum mechanics the binding of carbon dioxide to proteins is analyzed. It is concluded that acid/base interactions are the principal chemical force by which CO(2) is bound inside proteins. With respect to regular secondary structural elements, beta-sheets show a marked preference for CO(2) binding compared to alpha-helices. The data also support the inference that while either or both oxygens of CO(2) are generally tightly bound in the protein environment, the carbon is much less "sequestered." First principles and more approximate modeling techniques are assessed for quantifying CO(2) binding thermodynamics.

Effect of anesthetic structure on inhalation anesthesia: implications for the mechanism.

Many previous attempts (e.g., the Meyer-Overton hypothesis) to provide a single set of physical or chemical characteristics that accurately predict anesthetic potency have failed. A finding of a general predictive correlation would support the notion of a unitary theory of narcosis. Using the Abraham solvation parameter model, the minimum alveolar concentration, MAC, of 148 varied anesthetic agents can be fitted to a linear equation in log (1/MAC) with R(2) = 0.985 and a standard deviation, SD = 0.192 log units. Division of the 148 compounds into a training set and a test set shows that log (1/MAC) values can be predicted with no bias and with SD = 0.20 log units. The two main factors that determine MAC values are compound size and compound hydrogen bond acidity, both of which increase anesthetic activity. Shape has little or no effect on anesthetic activity. Our observations support a unitary theory of narcosis by inhalation anesthetics. A two-stage mechanism for inhalation anesthesia accounts for the observed structural effects of anesthetics. In this mechanism, the first main step is transfer of the anesthetic to the site of action, and the second step is interaction of the anesthetic with a receptor(s).

Nucleus Freedom North American clinical trial.

OBJECTIVE: To evaluate hearing outcomes and effects of stimulation rate on performance with the Nucleus Freedom cochlear implant (Cochlear Americas, Denver, CO). STUDY DESIGN AND SETTING: Randomized, controlled, prospective, single-blind clinical study using single-subject repeated measures (A-B-A-B) design at 14 academic centers in the United States and Canada and comparison with outcomes of a prior device by the same manufacturer. PATIENTS: Seventy-one severely/profoundly hearing impaired adults. RESULTS: Seventy-one adult recipients were randomly programmed in two different sets of rate: ACE or higher rate ACE RE. Mean scores for Consonant Nucleus Consonant words is 57%, Hearing in Noise Test (HINT) sentences in quiet 78%, and HINT sentences in noise 64%. Sixty-seven percent of subjects preferred slower rates of stimulation, and performance did not improve with higher rates of stimulation using this device. CONCLUSIONS: Subjects performed well, and there was no advantage to higher stimulation rates with this device. SIGNIFICANCE: Higher stimulation rates do not necessarily result in improved performance.

Conservation of residual acoustic hearing after cochlear implantation.

OBJECTIVE: This study was designed to test the hypothesis that partial hearing conservation is attainable after cochlear implantation with a long perimodiolar electrode. Surgical strategies for hearing conservation during cochlear implantation are described. STUDY DESIGN: Prospective, single-subject, repeated-measures design. SETTING: Academic tertiary care center. PATIENTS: Twenty-eight severely to profoundly hearing-impaired adult cochlear implant recipients who had some measurable hearing preoperatively. INTERVENTION: Cochlear implantation using Nucleus Freedom Contour Advance electrode. MAIN OUTCOME MEASURES: Preimplant and postimplant pure-tone thresholds and speech recognition scores were obtained to determine the incidence and degree of conserved hearing at a mean interval of 9 (+/-3.9) months. RESULTS: Thirty-two percent of subjects experienced complete conservation of hearing (0- to 10-dB loss), and 57% experienced partial conservation of hearing (>11 dB) after implantation. However, open-set speech recognition was partially conserved in only one subject. Cochlear implant performance was not better in patients with conservation of residual hearing. CONCLUSION: Conservation of pure-tone hearing was possible in 89% of implanted patients; however, residual speech perception was not conserved with this long perimodiolar electrode. A ceiling effect tends to inflate the prevalence of hearing conservation in implantation studies of severely to profoundly hearing-impaired patients.

Use of neural response telemetry measures to objectively set the comfort levels in the Nucleus 24 cochlear implant.

Cochlear implant programming necessitates accurate setting of programming levels, including maximum stimulation levels, of all active electrodes. Frequently, clinical techniques are adequate for setting these levels; however, they are sometimes insufficient (e.g., very young children). In the Nucleus 24, several methods have been suggested for estimation of comfort levels (C levels) from neural response telemetry (NRT); however, many require co-application of clinical measurements. Data was obtained from 21 adult Nucleus 24 recipients to develop reliable predictions of C levels. Multiple regression analysis was performed on NRT threshold, slope of the NRT growth function, age, length of deafness, length of cochlear implant use and electrode impedance to examine predictive ability. Only the NRT threshold and slope of the growth function measures were significant predictors yielding R2 values from 0.391 to 0.769. Results demonstrated that these measures may provide an alternative means of estimating C levels when other clinical measures are unavailable.

Objective methods in postlingually and prelingually deafened adults for programming cochlear implants: ESR and NRT.

This study compared responses of prelingually and postlingually deafened adult Nucleus 24 cochlear implant users on two objective measures employed to predict programming levels: neural response telemetry (NRT) and electrically evoked stapedial reflexes (eSR). Thirty experienced postlingually and prelingually deafened adult implant users underwent standard behavioural judgements of maximum comfortable loudness levels (C levels) and thresholds (Ts) followed by eSR and NRT measurements. Two different programs were created based on both the subjective judgement and the objective estimates of C levels (eSR thresholds) and these were compared. Relationships between the subjective and the objective measures were statistically analysed. Maximum stimulation levels estimated by both eSR and NRT were highly correlated with C levels. Variability of NRT results was higher than for eSR results. Mean NRT thresholds for postlingually deafened patients were higher than for prelingually deafened patients. A number of prelingually deafened users could distinguish no difference between programs; however, the majority of postlingually deafened users were sensitive to the difference and many reported preference for the program with eSR-estimated C levels. Neural response telemetry thresholds and eSRTs obtained in Nucleus 24 patients are highly correlated with C levels and Ts. Results suggest that estimation of C levels and Ts using NRT or eSR requires different correction factors for prelingually versus postlingually deafened adult subjects.

Facial nerve stimulation after cochlear implantation.

OBJECTIVES: This study was designed to compare the incidence and nature of facial nerve stimulation (FNS) in patients receiving cochlear implants (CI) manufactured by Cochlear Corporation, Advanced Bionics Corporation, and MedEl. STUDY DESIGN: Retrospective chart review at a tertiary referral center. METHODS: The charts of 600 patients who received CIs from 1993 to 2003 with at least 1 year of follow-up were reviewed for significant FNS (FNS on at least 1 channel at functional stimulation levels). Data collected included age, sex, etiology of deafness, device type, electrode, FNS onset after initial stimulation, number and location of electrode contacts causing FNS, and loudness level at which FSN occurred. Nucleus straight and perimodiolar electrodes were also compared. RESULTS: Thirty-nine of 600 (6.5%) patients had FNS on at least one channel, (MedEl 3 of 43 [7.0%], Nucleus 29 of 440 [6.6%], and Clarion 7 of 117 [6.0%]). The incidence of FNS in Nucleus perimodiolar electrodes (16 of 250 [6.4%]) was similar to straight electrodes (13 of 190 (6.8%]), as was the mean number of electrodes causing FNS per patient (11 vs. 12). However, straight electrodes caused stimulation at significantly softer perceived loudness levels than perimodiolar electrodes (P < .0001). CONCLUSIONS: In this large series of CI FNS, the overall incidence of FNS is consistent with previous reports. All devices had a similar incidence of FNS, but perimodiolar electrodes produced FNS only at significantly higher loudness levels than straight electrodes, making them preferable for patients at risk for FNS receiving Nucleus devices.