Taste masking pharmaceutical excipients and their applications / 药学学报

The taste of drugs has an important impact on the compliance of patients, but most of the active drug ingredients have an uncomfortable taste, especially traditional Chinese medicine. Through a variety of pharmaceutical excipients with taste masking properties combined with corresponding technologies can improve the taste of drugs and the characteristics of other dosage forms, so as to improve patient compliance. Here, we mainly summarize the auxiliary materials used for taste masking, explain the mechanism of taste masking from the point of view of excipients and introduces related uses, so as to provide reference for further research on taste masking of pediatric preparations.

[Combined anti-bitterness strategy for extremely bitter characteristics of Andrographis Herba decoction and mechanism].

Three kinds of excipients were selected to investigate the anti-bitterness effect on the extremely bitter characteristics of Andrographis Herba decoction, and the optimal combined anti-bitterness formula was obtained. The preparation principle of different excipients was clarified by virtual screening and experimental verification to explore the advantages of the three kinds of excipients in the combined anti-bitterness effect. Sensory evaluation showed that mPEG_(2000)-PLLA_(2000), γ-cyclodextrin(γ-CD), and aspartame all had good anti-bitterness effect, which reduced the bitterness intensity of Andrographis Herba decoction by 0.5, 6, and 3 points, respectively. The anti-bitterness effect was superior when 0.15% mPEG_(2000)-PLLA_(2000), 1.60% γ-CD, and 0.04% aspartame were combined, and the taste score of the Andrographis Herba decoction decreased from 8 points(severe bitterness) to 1 point(almost no bitterness). Quantum chemistry calculations showed that mPEG_(2000)-PLLA_(2000) reduced the electrostatic potential of bitter groups, which spontaneously combined with it and formed a physical barrier, hindering the binding of bitter components to receptors. The interaction between γ-CD and bitter components was studied. It was found that the surface area and free energy of γ-CD decreased and the dipole moment increased, indicating that γ-CD included bitter components and self-assembled to form supramolecules. Molecular docking showed that hydroxy at position 14 and carbonyl at position 16 of andrographolide, and hydroxy at position 3 and 4, carbonyl at position 14, and five-membered lactone ring of dehydrated andrographolide were possibly the main bitter groups. The binding free energies of aspartame to bitter receptors TAS2 R10, TAS2 R14, and TAS2 R46 were-3.21,-1.55, and-2.52 kcal·mol~(-1), respectively, indicating that aspartame competed to inhibit the binding of bitter groups to bitter receptors. The results of content determination showed that the free amounts of andrographolide and dehydrated andrographolide in Andrographis Herba decoction were 0.23% and 0.28% respectively, while after adding flavor masking excipients, the dissociation amount of andrographolide and dehydrated andrographolide in the decoction decreased to 0.13% and 0.20%, respectively. The above results show that mPEG_(2000)-PLLA_(2000) involves some bitter components into it through micellar self-assembly to reconcile the entrance bitterness, and γ-CD includes the remaining bitter components in the real solution to control the main bitter taste. Aspartame further competes to inhibit the combination of bitter components and bitter receptors, and improves the taste to be sweet. Multi-excipients combined with anti-bitterness strategy significantly reduces the free concentration of bitter substances in Andrographis Herba decoction, and optimizes the taste of the decoction.

[Main spicy components, mechanism and masking technology for spicy flavor of Chinese medicine: a review].

Many Chinese medicinal materials, vegetable oils and extracts, and even Chinese patent medicines are spicy, which influences the medication compliance of patients, especially children. Different from the sour, sweet, bitter, salty, and umami tastes, it is a painful sensation formed when the spicy substances stimulate the nerve endings. At the moment, there are a few studies on the spicy components and mechanism and masking technology for the spicy flavor of Chinese medicine in the pharmaceutical industry, and the findings in food science are usually taken as a reference, which fail to guide the masking of the spicy flavor in Chinese medicine preparations. According to literature research, the exterior-releasing medicine, dampness-resolving medicine, and interior-warming medicine are spicy, especially some vegetable oils and extracts. Taking Zingiberis Rhizoma and prescriptions containing this medicinal as an example, the spicy components in Chinese medicine and the structure-activity characteristics were analyzed to reveal the mechanism for the spicy flavor: spicy components activate the transient receptor potential vanilloid subfamily member 1(TRPV1). The advantages and disadvantages of separation, neutralization with sugar, and inclusion for the masking of the spicy flavor were summarized and the applicability in Chinese medicine was analyzed. Moreover, the future development direction was put forward. This study is expected to promote the development of spicy masking technology for Chinese medicine prescriptions for children.

[Key techniques for granulation and flavor masking of innovative Chinese medicinal preparations for children: a review].

There are many kinds of pharmaceutical preparations for children in China, which are generally divided into oral solid preparations and oral liquid preparations. Solid preparations, such as microtablets, pellets, dispersible tablets, and fine granules, have become the development trend of pediatric drugs. Liquid preparations mainly include syrup, suspension, oral solution, and drops. The poor taste and the treatment of drugs in children of different ages are the key factors affecting the efficacy, safety, and compliance of pediatric drugs. To reduce the risk caused by the fluctuation of blood concentration and improve the oral compliance of pediatric drugs, it is urgent to develop new techniques for granulation and flavor maskingto improve the poor taste of solid preparations. For liquid pre-parations with poor taste, the flavor correction technique should be used. This paper summarized the new pharmaceutical techniques for granulation and flavor masking, and it was found that sustained/controlled-releasegranules, fine granules, and chewing solid mini-tablets became the mainstream of oral solid preparations for children. Generally, multiparticle preparation, coating, microencapsulation, and other granulating techniques were involved in these preparations. Granulation and flavor masking are closely related and synergetic. Flavor masking techniques mask the bitter taste of Chinese medicine from four aspects, including confusing the brain taste, changing the compounds, reducing the exposure of bitter molecules to bitter receptors in the mouth, and numbing the taste cells to increase the threshold of bitter perception. At present, the main drugs for children on the market mainly inhibit the oral release of bitter drugs.

The Taste-Masking Mechanism of Chitosan at the Molecular Level on Bitter Drugs of Alkaloids and Flavonoid Glycosides from Traditional Chinese Medicine.

Taste masking of traditional Chinese medicines (TCMs) containing multiple bitter components remains an important challenge. In this study, berberine (BER) in alkaloids and phillyrin (PHI) in flavonoid glycosides, which are common bitter components in traditional Chinese medicines, were selected as model drugs. Chitosan (CS) was used to mask their unfriendly taste. Firstly, from the molecular level, we explained the taste-masking mechanism of CS on those two bitter components in detail. Based on those taste-masking mechanisms, the bitter taste of a mixture of BER and PHI was easily masked by CS in this work. The physicochemical characterization results showed the taste-masking compounds formed by CS with BER (named as BER/CS) and PHI (named as PHI/CS) were uneven in appearance. The drug binding efficiency of BER/CS and PHI/CS was 50.15 ± 2.63% and 67.10 ± 2.52%, respectively. The results of DSC, XRD, FTIR and molecular simulation further indicated that CS mainly masks the bitter taste by disturbing the binding site of bitter drugs and bitter receptors in the oral cavity via forming hydrogen bonds between its hydroxyl or amine groups and the nucleophilic groups of BER and PHI. The taste-masking evaluation results by the electronic tongue test confirmed the excellent taste-masking effects on alkaloids, flavonoid glycosides or a mixture of the two kinds of bitter components. The in vitro release as well as in vivo pharmacokinetic results suggested that the taste-masked compounds in this work could achieve rapid drug release in the gastric acid environment and did not influence the in vivo pharmacokinetic results of the drug. The taste-masking method in this work may have potential for the taste masking of traditional Chinese medicine compounds containing multiple bitter components.

Dynamic Masking: A Proposal of Burden-Based Metrics for Masking in K-12 Schools During the COVID-19 Pandemic.

BACKGROUND: Ongoing masking of K-12 children has not been universally accepted despite recommendation from public health authorities. In states without universal mask mandates for schools, district administrators are forced to make masking decisions under significant local political pressures. There is a call for endpoints to masking to allow communities to tailor mitigation while keeping schools safe, focusing on harm reduction. METHODS: We reviewed existing measures for the safe opening of schools and designed a stepwise, accessible approach to the removal of masks in the K-12 setting. RESULTS: Focusing first on the assessment of school impact due to COVID-19 disease and then considering the context of existing community transmission levels allows for a metrics-based approach to masking that is flexible and practical, enabling school officials to adapt quickly to the pandemic landscape in their communities, independent of political pressures. CONCLUSIONS: While this proposal is preliminary, a dynamic metric system for masking may encourage those communities who wish to minimize masking to adopt masks during highest risk periods, protecting against SARS-CoV-2 transmission in schools and allowing for more holistic harm reduction. This approach may serve to guide districts during times of uncertainty when central guidance short of universal masking is lacking.

Effect of antiepileptic drug levetiracetam on cochlear function.

BACKGROUND: Levetiracetam (LEV, 5-100 mg/kg) has been shown to prevent audiogenic seizures in a dose-dependent manner. This chemical is known to bind to synaptic vesicle protein 2A and inhibit l-type calcium channels, affecting neurotransmitter release. We hypothesize that the drug prevents audiogenic seizures partially by affecting cochlear neural response. METHODS: To test this hypothesis, rats were given 1000, 500, 50, or 0 mg/kg (saline control) LEV-injection. Distortion product otoacoustic emissions (DPOAE), reflecting outer hair cell (OHC) function, and cochlear compound action potentials (CAP), reflecting cochlear neural output, were recorded and compared pre- and post-LEV. RESULTS: 1000 mg/kg LEV-injection did not significantly affect DPOAE. The high dose LEV-injection, however, significantly reduced CAP amplitude resulting threshold shift (TS), prolonged CAP latency, and enhanced CAP forward masking. CAP latency and forward masking were significantly affected at the 500 mg/kg dose, but CAP-TS remained unchanged after LEV-injection. Interestingly, CAP latency wassignificantly prolonged, at least at the low stimulation levels, although the amplitude of CAP remained constant after a clinical dose of LEV-injection (50 mg/kg). DISCUSSION: Since the clinical dose of LEV-injection does not reduce CAP amplitude, the reduction of cochlear neural output is unlikely to be the underlying mechanism of LEV in the treatment of audiogenic seizure. The delayed cochlear neural response may be partially related to the prevention of audiogenic seizure. However, neuropharmacological changes in the central nervous system must play a major role in the treatment of audiogenic seizure, as it does in the treatment of focal epilepsy.

Improving reading skills in children with dyslexia: efficacy studies on a newly proposed remedial intervention-repeated reading with vocal music masking (RVM).

In this work, two different studies are examined to evaluate the effectiveness of a novel intervention program for the improvement of reading ability in children with dyslexia, known as repeated reading with vocal music masking (RVM). The proposed remedial approach is inspired by Breznitz's original work. The studies assess a 5-week program of intensive RVM training in a pre-post-test clinical paradigm, as well as a longitudinal paradigm where it is compared to 8 months of the standard remediation program (SRP). The results of both studies support the efficacy of the newly proposed RVM method. Notably in the longitudinal study, the reading speed of children, as well as related phonological, visuo-attentional, and cognitive skills, and attitudes toward reading, were measured regularly. Significant improvements in reading efficiency and related skills were observed, as well as greater motivation to read after RVM training. A modeling of the data specifically linked executive and processing speed skills to be involved in RVM training, suggesting that RVM may help rebalance the phonological and orthographic coding procedures necessary for efficient reading. The short, intensive, and focused nature of RVM training makes it a viable and attractive intervention for clinical practice. As preliminary results are promising, RVM training may prove to be a valuable tool that clinicians can call upon to effectively treat reading fluency disorders, especially when standard programs do not provide results.

Neurophysiology goes wild: from exploring sensory coding in sound proof rooms to natural environments.

To perform adaptive behaviours, animals have to establish a representation of the physical "outside" world. How these representations are created by sensory systems is a central issue in sensory physiology. This review addresses the history of experimental approaches toward ideas about sensory coding, using the relatively simple auditory system of acoustic insects. I will discuss the empirical evidence in support of Barlow's "efficient coding hypothesis", which argues that the coding properties of neurons undergo specific adaptations that allow insects to detect biologically important acoustic stimuli. This hypothesis opposes the view that the sensory systems of receivers are biased as a result of their phylogeny, which finally determine whether a sound stimulus elicits a behavioural response. Acoustic signals are often transmitted over considerable distances in complex physical environments with high noise levels, resulting in degradation of the temporal pattern of stimuli, unpredictable attenuation, reduced signal-to-noise levels, and degradation of cues used for sound localisation. Thus, a more naturalistic view of sensory coding must be taken, since the signals as broadcast by signallers are rarely equivalent to the effective stimuli encoded by the sensory system of receivers. The consequences of the environmental conditions for sensory coding are discussed.

Effects of spatial separation with better- ear listening on N1-P2 complex.

OBJECTIVE: The purpose of this study was to determine better- ear listening effect on spatial separation with the N1-P2 complex. METHODS: Twenty individuals with normal hearing participated in this study. The speech stimulus /ba/ was presented in front of the participant (0°). Continuous Speech Noise (5 dB signal-to-noise ratio) was presented either in front of the participant (0°), left-side (-90°), or right-side (+90°). N1- P2 complex has been recorded in quiet and three noisy conditions. RESULTS: There was a remarkable effect of noise direction on N1, P2 latencies. When the noise was separated from the stimulus, N1 and P2 latency increased in terms of when noise was co-located with the stimulus. There was no statistically significant difference in N1-P2 amplitudes between the stimulus-only and co-located condition. N1-P2 amplitude was increased when the noise came from the sides, according to the stimulus-only and co-located conditions. CONCLUSION: These findings demonstrate that the latency shifts on N1-P2 complex explain cortical mechanisms of spatial separation in better-ear listening.

[Review of taste masking techniques in Chinese patent medicine].

Single herbs and Chinese patent medicine preparations often have bad taste, such as bitterness and astringency, which is one of the key factors affecting patients' medication compliance, and would affect the therapeutic effect and restrict the extensive application in clinical practice. Therefore, how to make use of taste masking techniques to improve the bad taste of traditional Chinese medicines has become an important project. Through the collection and summarization of Chinese and foreign journals and papers in recent years, this paper discussed the generation mechanism of bitter taste, the new methods of masking bitter taste and the evaluation me-thods of bitter taste, in order to provide references for the taste masking of Chinese patent medicines preparations.

Review of taste masking techniques in Chinese patent medicine / 中国中药杂志

Single herbs and Chinese patent medicine preparations often have bad taste, such as bitterness and astringency, which is one of the key factors affecting patients' medication compliance, and would affect the therapeutic effect and restrict the extensive application in clinical practice. Therefore, how to make use of taste masking techniques to improve the bad taste of traditional Chinese medicines has become an important project. Through the collection and summarization of Chinese and foreign journals and papers in recent years, this paper discussed the generation mechanism of bitter taste, the new methods of masking bitter taste and the evaluation me-thods of bitter taste, in order to provide references for the taste masking of Chinese patent medicines preparations.

Jet Lag Recovery and Memory Functions Are Correlated with Direct Light Effects on Locomotion.

Jet lag is a circadian disruption that affects millions of people, resulting, among other things, in extreme sleepiness and memory loss. The hazardous implications of such effects are evident in situations in which focus and attention are required. Remarkably, there is a limited understanding of how jet lag recovery and associated memory loss vary year round under different photoperiods. Here we show, using different cycles representing winter, summer, and equinox in male mice, that jet lag recovery and memory vary significantly with photoperiod changes. We uncover a positive correlation of acute light effects on circadian-driven locomotion (known as negative masking) with photoentrainment speed and memory enhancement during jet lag. Specifically, we show that enhancing or reducing negative masking is correlated with better or worse memory performance, respectively. This study indicates that in addition to timed-light exposure for phase shifting, the negative masking response could also be biologically relevant when designing effective treatments of jet lag.

[Structure-activity relationship of coptis alkaloid bitterness inhibited by mPEG-PLLA].

Inhibition of bitterness is a significant measure to improve the compliance and clinical efficacy of traditional Chinese medicine(TCM) decoction. According to the characteristics of TCM decoction, such as high dispersion of bitterness components, multi-component bitterness superposition and strong instantaneous stimulation, the research group put forward a new strategy to inhibit bitterness in the early stage based on the self-assembly characteristics of amphiphilic substances in aqueous solution, in order to reduce the distribution of bitterness components in real solution and achieve the purpose of bitter-masking. It was found that the bitter-masking effect of amphiphilic substances was different on the bitter compounds of various structures. Therefore, it was speculated that there might be a certain relationship between the bitter inhibition effect and the substrate structure. In this paper, the interaction between mPEG-PLLA and five bitter alkaloids(bamatine, jatrorrhizine, berberine, epiberberine and coptisine) in Coptidis Rhizoma was studied to explore the effect of substrate structure on the inhibition of bitterness. The sensory test of volunteers was used to determine the bitter-masking effect of mPEG-PLLA on the decoction of Coptidis Rhizoma and its main bitter alkaloids. The molecular docking and molecular force field were applied to locate the bitter groups and the bitter-masking parts. The relationship between the bitter strength and the structure was analyzed by the surface electrostatic potential of the bitter alkaloids, and the correlation between the bitter-masking effect and the structural parameters of the bitter components was explored by factor analysis, so as to clarify the structure-activity relationship of mPEG-PLLA in masking the bitterness of coptis alkaloids. It was found that mPEG-PLLA had significant taste masking effect on the decoction of Coptidis Rhizoma and five alkaloids. The masking effect was obviously related to the structure of different alkaloids: the effect increased with the increase of the number of hydrogen donors, rotatable bonds, molecular weight, and hydrophobicity, and decreased with the increase of surface electrostatic potential, electrophilicity and binding energy with bitter receptors. In this study, the influence of alkaloid structure of Coptidis Rhizoma on the butter-masking effect of mPEG-PLLA was preliminarily elucidated, providing a scientific basis for better exerting the bitter-masking effect of amphiphilic block copolymers.

A field study of auditory sensitivity of the Atlantic puffin, Fratercula arctica.

Hearing is vital for birds as they rely on acoustic communication with parents, mates, chicks and conspecifics. Amphibious seabirds face many ecological pressures, having to sense cues in air and underwater. Natural noise conditions have helped shape this sensory modality but anthropogenic noise is increasingly impacting seabirds. Surprisingly little is known about their hearing, despite their imperiled status. Understanding sound sensitivity is vital when we seek to manage the impacts of man-made noise. We measured the auditory sensitivity of nine wild Atlantic puffins, Fratercula arctica, in a capture-and-release setting in an effort to define their audiogram and compare these data with the hearing of other birds and natural rookery noise. Auditory sensitivity was tested using auditory evoked potential (AEP) methods. Responses were detected from 0.5 to 6 kHz. Mean thresholds were below 40 dB re. 20 µPa from 0.75 to 3 kHz, indicating that these were the most sensitive auditory frequencies, similar to other seabirds. Thresholds in the 'middle' frequency range 1-2.5 kHz were often down to 10-20 dB re. 20 µPa. The lowest thresholds were typically at 2.5 kHz. These are the first in-air auditory sensitivity data from multiple wild-caught individuals of a deep-diving alcid seabird. The audiogram was comparable to that of other birds of similar size, thereby indicating that puffins have fully functioning aerial hearing despite the constraints of their deep-diving, amphibious lifestyles. There was some variation in thresholds, yet animals generally had sensitive ears, suggesting aerial hearing is an important sensory modality for this taxon.

[Progress on formation and taste-masking technology of stench of animal medicines].

Animal medicines have been called "medicine with affinity to flesh and blood" by doctors of all ages, which always act as an important branch of Chinese medicine. They have various types, extensive sources and long application history, with unique cli-nical effects in anti-coagulation, anti-thrombosis, anti-fatigue, immune regulation, anti-tumor, anti-convulsion and so on. Most animal medicines contain proteins, fatty acids, and trimethylamine oxides, which are prone to decomposition and produce substances such as biological amines, aldehydes, ketones, alcohols, trimethylamine and ammonia with unpleasant odors. The stench produced by the combination of various odors can easily cause side effects such as nausea and vomiting, which would probably affect the drug compliance and clinical efficacy in patients, and block the development of high-quality animal medicines. At present, we have insufficient understanding on sources and formation mechanism of the stench of animal medicines, lacking development of taste-masking technology. Therefore, the universality, formation, vomiting mechanism, evaluation methods, and masking technology of stench of animal medicines were summarized in this paper, so as to deepen the recognition of stench, provide references for the development of animal medicines deodorization technology, enhance patients' compliance with animal medicines, and promote animal drugs to better serve public health in the new era.

Noise-Sensitive But More Precise Subcortical Representations Coexist with Robust Cortical Encoding of Natural Vocalizations.

Humans and animals maintain accurate sound discrimination in the presence of loud sources of background noise. It is commonly assumed that this ability relies on the robustness of auditory cortex responses. However, only a few attempts have been made to characterize neural discrimination of communication sounds masked by noise at each stage of the auditory system and to quantify the noise effects on the neuronal discrimination in terms of alterations in amplitude modulations. Here, we measured neural discrimination between communication sounds masked by a vocalization-shaped stationary noise from multiunit responses recorded in the cochlear nucleus, inferior colliculus, auditory thalamus, and primary and secondary auditory cortex at several signal-to-noise ratios (SNRs) in anesthetized male or female guinea pigs. Masking noise decreased sound discrimination of neuronal populations in each auditory structure, but collicular and thalamic populations showed better performance than cortical populations at each SNR. In contrast, in each auditory structure, discrimination by neuronal populations was slightly decreased when tone-vocoded vocalizations were tested. These results shed new light on the specific contributions of subcortical structures to robust sound encoding, and suggest that the distortion of slow amplitude modulation cues conveyed by communication sounds is one of the factors constraining the neuronal discrimination in subcortical and cortical levels.SIGNIFICANCE STATEMENT Dissecting how auditory neurons discriminate communication sounds in noise is a major goal in auditory neuroscience. Robust sound coding in noise is often viewed as a specific property of cortical networks, although this remains to be demonstrated. Here, we tested the discrimination performance of neuronal populations at five levels of the auditory system in response to conspecific vocalizations masked by noise. In each acoustic condition, subcortical neurons better discriminated target vocalizations than cortical ones and in each structure, the reduction in discrimination performance was related to the reduction in slow amplitude modulation cues.

The effect of a coding strategy that removes temporally masked pulses on speech perception by cochlear implant users.

Speech recognition in noisy environments remains a challenge for cochlear implant (CI) recipients. Unwanted charge interactions between current pulses, both within and between electrode channels, are likely to impair performance. Here we investigate the effect of reducing the number of current pulses on speech perception. This was achieved by implementing a psychoacoustic temporal-masking model where current pulses in each channel were passed through a temporal integrator to identify and remove pulses that were less likely to be perceived by the recipient. The decision criterion of the temporal integrator was varied to control the percentage of pulses removed in each condition. In experiment 1, speech in quiet was processed with a standard Continuous Interleaved Sampling (CIS) strategy and with 25, 50 and 75% of pulses removed. In experiment 2, performance was measured for speech in noise with the CIS reference and with 50 and 75% of pulses removed. Speech intelligibility in quiet revealed no significant difference between reference and test conditions. For speech in noise, results showed a significant improvement of 2.4 dB when removing 50% of pulses and performance was not significantly different between the reference and when 75% of pulses were removed. Further, by reducing the overall amount of current pulses by 25, 50, and 75% but accounting for the increase in charge necessary to compensate for the decrease in loudness, estimated average power savings of 21.15, 40.95, and 63.45%, respectively, could be possible for this set of listeners. In conclusion, removing temporally masked pulses may improve speech perception in noise and result in substantial power savings.

Insect repellents mediate species-specific olfactory behaviours in mosquitoes.

BACKGROUND: The species-specific mode of action for DEET and many other mosquito repellents is often unclear. Confusion may arise for many reasons. First, the response of a single mosquito species is often used to represent all mosquito species. Second, behavioural studies usually test the effect of repellents on mosquito attraction towards human odorants, rather than their direct repulsive effect on mosquitoes. Third, the mosquito sensory neuron responses towards repellents are often not directly examined. METHODS: A close proximity response assay was used to test the direct repulsive effect of six mosquito repellents on Anopheles coluzzii, Aedes aegypti and Culex quinquefasciatus mosquitoes. Additionally, the behavioural assay and calcium imaging recordings of antennae were used to test the response of An. coluzzii mosquitoes towards two human odorants (1-octen-3-ol and benzaldehyde) at different concentrations, and mixtures of the repellents lemongrass oil and p-menthane-3,8-diol (PMD) with DEET. RESULTS: Anopheles coluzzii mosquitoes were repelled by lemongrass oil and PMD, while Ae. aegypti and Cx. quinquefasciatus mosquitoes were repelled by lemongrass oil, PMD, eugenol, and DEET. In addition, high concentrations of 1-octen-3-ol and benzaldehyde were repellent, and activated more olfactory receptor neurons on the An. coluzzii antennae than lower concentrations. Finally, changes in olfactory responses to repellent mixtures reflected changes in repulsive behaviours. CONCLUSIONS: The findings described here suggest that different species of mosquitoes have different behavioural responses to repellents. The data further suggest that high-odour concentrations may recruit repellent-sensing neurons, or generally excite many olfactory neurons, yielding repellent behavioural responses. Finally, DEET can decrease the neuronal and behavioural response of An. coluzzii mosquitoes towards PMD but not towards lemongrass oil. Overall, these studies can help inform mosquito repellent choice by species, guide decisions on effective repellent blends, and could ultimately identify the olfactory neurons and receptors in mosquitoes that mediate repellency.

Forward masking patterns by low and high-rate stimulation in cochlear implant users: Differences in masking effectiveness and spread of neural excitation.

The goal of the present study was to compare forward masking patterns by stimulation of low and high rates in cochlear implant users. Postlingually deafened Cochlear Nucleus® device users participated in the study. In experiment 1, two maskers of different rates (250 and 1000 pulses per second) were set at levels that produced equal masking for a probe presented at the same electrode as the maskers. This aligned the two masking functions at the on-site probe location. Then their forward masking patterns for the far probes were compared. Results showed that slope of the masked probe-threshold decay as a function of probe-masker separation was steeper for the high-rate than the low-rate masker. A linear model indicated that this difference in spread of neural excitation (SOE) was accounted for by two factors that were not correlated with each other. One factor was that the low-rate masker required a considerably higher current level to be equally effective in masking as the high-rate masker. The second factor was the effect of stimulation rate on loudness, i.e., integration of multiple pulses. This was consistent with our hypothesis that if an increase in stimulation rate does not result in an increased total neural response, then it is unlikely that the change in rate would change spatial distribution of the neural activity. Interestingly, the difference in masking effectiveness of the maskers predicted subjects' speech recognition. Poorer performers were those who showed more comparable masking effects by maskers of different rates. The difference in the masking effectiveness may indirectly measure the auditory neurons' excitability, which predicts speech recognition. In experiment 2, SOE of the high-rate and low-rate maskers were compared at a level that is clinically relevant, i.e., equal loudness. At equal loudness, high-rate stimulation not only produced an overall greater amount of forward masking, but also a shallower decay of masking with probe-masker separation (wider SOE), compared to low rate. The difference in SOE was the opposite to the findings from experiment 1. Whether the maskers were calibrated for equal masking or loudness, the absolute current level was always higher for the low-rate masker, which suggests that the SOE patterns cannot be explained by current spread alone. The fact that high-rate stimulation produced greater masking and wider SOE at equal loudness may explain why using high stimulation rates has not produced consistent benefits for speech recognition, and why lowering stimulation rate from the manufacturer's default sometimes results in improved speech recognition for subjects.