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Objectives: Sensorineural hearing loss is common with advancing age, but even when hearing is normal or near normal in older persons, performance deficits are often seen for suprathreshold listening tasks such as understanding speech in background noise or localizing the direction sounds are coming from. This suggests there is also a more central source of the problem. Objectives of this study were to examine as a function of age (young adult to septuagenarian) performance on: 1) a spatial acuity task examining lateralization ability, and a spatial speech-in-noise (SSIN) recognition task, both measured in a hemi-anechoic sound field using a circular horizontal-plane loudspeaker array, and 2) a suprathreshold auditory temporal processing task and a spectro-temporal processing task, both measured under headphones. Further, we examined any correlations between the measures. Design: Subjects were 48 adults, aged 21 to 78, with either normal hearing or only a mild sensorineural hearing loss through 4000 Hz. The lateralization task measured minimum audible angle (MAA) for 500 and 4000 Hz narrowband noise (NBN) bursts in diffuse background noise for both an on-axis (subject facing 0°) and off-axis (facing 45°) listening condition at signal-to-noise ratios (SNRs) of -3, -6, -9, and -12 dB. For 42 of the subjects, SSIN testing was also completed for key word recognition in sentences in multi-talker babble noise; specifically, the separation between speech and noise loudspeakers was adaptively varied to determine the difference needed for 40% and 80% correct performance levels. Finally, auditory temporal processing ability was examined using the Temporal Fine Structure test (44 subjects), and the Spectro-Temporal Modulation test (46 subjects). Results: Mean lateralization performances were poorer (larger MAAs) in older compared to younger subjects, particularly in the more adverse listening conditions (i.e., for 4000 Hz, off-axis, and at poorer SNRs). Performance variability was notably higher for older subjects than for young adults. The 4000 Hz NBN bursts produced larger MAAs than did 500 Hz NBN bursts. The SSIN data also showed declining mean performance with age at both criterion levels, with greater variability again found for older subjects. Spearman rho analyses revealed some low to moderate, but significant correlation coefficients for age versus MAA and for age versus SSIN results. Results from both the TFS and STM showed decreased mean performance with aging, and revealed moderate, significant correlations, with the strongest relationship shown with the TFS test. Finally, of note, extended-high-frequency (EHF) hearing loss (measured between 9000 and 16,000 Hz) was found to increase with aging, but was not seen in the young adult subjects. Conclusions: Particularly for more adverse listening conditions, age-related deficits were found on both of the spatial hearing tasks and in temporal and spectro-temporal processing abilities. It may be that deficits in temporal processing ability contribute to poorer spatial hearing performance in older subjects due to inaccurate coding of binaural/interaural timing information sent from the periphery to the brainstem. In addition, EHF hearing loss may be a coexisting factor that impacts performance in older subjects.
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Vocalisations are increasingly being recognised as an important aspect of normal rodent behaviour yet little is known of how they interact with other spontaneous behaviours such as sleep and torpor, particularly in a social setting. We obtained chronic recordings of the vocal behaviour of adult male and female Djungarian hamsters (Phodopus sungorus) housed under short photoperiod (8 h light, 16 h dark, square wave transitions), in different social contexts. The animals were kept in isolation or in same-sex sibling pairs, separated by a grid which allowed non-physical social interaction. On approximately 20% of days hamsters spontaneously entered torpor, a state of metabolic depression that coincides with the rest phase of many small mammal species in response to actual or predicted energy shortages. Animals produced ultrasonic vocalisations (USVs) with a peak frequency of 57 kHz in both social and asocial conditions and there was a high degree of variability in vocalisation rate between subjects. Vocalisation rate was correlated with locomotor activity across the 24-h light cycle, occurring more frequently during the dark period when the hamsters were more active and peaking around light transitions. Solitary-housed animals did not vocalise whilst torpid and animals remained in torpor despite overlapping with vocalisations in social-housing. Besides a minor decrease in peak USV frequency when isolated hamsters were re-paired with their siblings, changing social contexts did not influence vocalisation behaviour or structure. In rare instances, temporally overlapping USVs occurred when animals were socially-housed and were grouped in such a way that could indicate coordination. We did not observe broadband calls (BBCs) contemporaneous with USVs in this paradigm, corroborating their correlation with physical aggression which was absent from our experiment. Overall, we find little evidence to suggest a direct social function of hamster USVs. We conclude that understanding the effects of vocalisations on spontaneous behaviours, such as sleep and torpor, will inform experimental design of future studies, especially where the role of social interactions is investigated.
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Ritmo Circadiano , Phodopus , Fotoperiodo , Vocalización Animal , Animales , Vocalización Animal/fisiología , Masculino , Phodopus/fisiología , Femenino , Ritmo Circadiano/fisiología , Cricetinae , Actividad Motora/fisiología , Fenotipo , Letargo/fisiología , Ultrasonido , Estaciones del Año , Conducta SocialRESUMEN
Aims: Scoliosis is a lateral curvature of the spine with associated rotation, often causing distress due to appearance. For some curves, there is good evidence to support the use of a spinal brace, worn for 20 to 24 hours a day to minimize the curve, making it as straight as possible during growth, preventing progression. Compliance can be poor due to appearance and comfort. A night-time brace, worn for eight to 12 hours, can achieve higher levels of curve correction while patients are supine, and could be preferable for patients, but evidence of efficacy is limited. This is the protocol for a randomized controlled trial of 'full-time bracing' versus 'night-time bracing' in adolescent idiopathic scoliosis (AIS). Methods: UK paediatric spine clinics will recruit 780 participants aged ten to 15 years-old with AIS, Risser stage 0, 1, or 2, and curve size (Cobb angle) 20° to 40° with apex at or below T7. Patients are randomly allocated 1:1, to either full-time or night-time bracing. A qualitative sub-study will explore communication and experiences of families in terms of bracing and research. Patient and Public Involvement & Engagement informed study design and will assist with aspects of trial delivery and dissemination. Discussion: The primary outcome is 'treatment failure' (Cobb angle progression to 50° or more before skeletal maturity); skeletal maturity is at Risser stage 4 in females and 5 in males, or 'treatment success' (Cobb angle less than 50° at skeletal maturity). The comparison is on a non-inferiority basis (non-inferiority margin 11%). Participants are followed up every six months while in brace, and at one and two years after skeletal maturity. Secondary outcomes include the Scoliosis Research Society 22 questionnaire and measures of quality of life, psychological effects of bracing, adherence, anxiety and depression, sleep, satisfaction, and educational attainment. All data will be collected through the British Spine Registry.
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Purpose: Purinergic signaling pathways activated by extracellular ATP have been implicated in the regulation of lens volume and transparency. In this study, we investigated the location of ATP release from whole rat lenses and the mechanism by which osmotic challenge alters such ATP release. Methods: Three-week-old rat lenses were cultured for 1 h in isotonic artificial aqueous humor (AAH) with no extracellular Ca2+, hypotonic AAH, or hypertonic AAH. The hypotonic AAH-treated lenses were also cultured in the absence or presence of connexin hemichannels and the pannexin channel blockers carbenoxolone, probenecid, and flufenamic acid. The ATP concentration in the AAH was determined using a Luciferin/luciferase bioluminescence assay. To visualize sites of ATP release induced by hemichannel and/or pannexin opening, the lenses were cultured in different AAH solutions, as described above, and incubated in the presence of Lucifer yellow (MW = 456 Da) and Texas red-dextran (MW = 10 kDa) for 1 h. Then the lenses were fixed, cryosectioned, and imaged using confocal microscopy to visualize areas of dye uptake from the extracellular space. Results: The incubation of the rat lenses in the AAH that lacked Ca2+ induced a significant increase in the extracellular ATP concentration. This was associated with an increased uptake of Lucifer yellow but not of Texas red-dextran in a discrete region of the outer cortex of the lens. Hypotonic stress caused a similar increase in ATP release and an increase in the uptake of Lucifer yellow in the outer cortex, which was significantly reduced by probenecid but not by carbenoxolone or flufenamic acid. Conclusions: Our data suggest that in response to hypotonic stress, the intact rat lens is capable of releasing ATP. This seems to be mediated via the opening of pannexin channels in a specific zone of the outer cortex of the lens. Our results support the growing evidence that the lens actively regulates its volume and therefore, its optical properties, via puerinergic signaling pathways.
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Carbenoxolona , Probenecid , Ratas , Animales , Probenecid/farmacología , Carbenoxolona/farmacología , Ácido Flufenámico , Dextranos , Conexinas/metabolismo , Adenosina Trifosfato/metabolismoRESUMEN
BACKGROUND: Speech discrimination assessments are used to validate amplification fittings of older children who are hard of hearing (CHH). Unfortunately, speech discrimination is not assessed clinically ≤24 months and in turn no studies have investigated the relationship between speech discrimination during infancy and later language development among CHH. OBJECTIVE: To examine the relationship between an individual infant's speech discrimination measured at 9 months and their expressive/receptive spoken language at 30 months for children with normal hearing (CNH) and CHH. METHODS: Behavioral speech discrimination was assessed at 9 months and language assessments were conducted at 16, 24, and 30 months using a parent questionnaire, and at 30 months using the Mullen Scales of Early Learning among 90 infants (49 CNH; 41 CHH). RESULTS: Conditioned Head Turn (CHT) performance for /a-i/ significantly predicted expressive and receptive language at 30 months across both groups. Parental questionnaires were also predictive of later language ability. No significant differences in speech discrimination or language outcomes between CNH and CHH were found. CONCLUSIONS: This is the first study to document a positive relationship between infant speech discrimination and later language abilities in both early-identified CHH and CNH.
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In almost every natural environment, sounds are reflected by nearby objects, producing many delayed and distorted copies of the original sound, known as reverberation. Our brains usually cope well with reverberation, allowing us to recognize sound sources regardless of their environments. In contrast, reverberation can cause severe difficulties for speech recognition algorithms and hearing-impaired people. The present study examines how the auditory system copes with reverberation. We trained a linear model to recover a rich set of natural, anechoic sounds from their simulated reverberant counterparts. The model neurons achieved this by extending the inhibitory component of their receptive filters for more reverberant spaces, and did so in a frequency-dependent manner. These predicted effects were observed in the responses of auditory cortical neurons of ferrets in the same simulated reverberant environments. Together, these results suggest that auditory cortical neurons adapt to reverberation by adjusting their filtering properties in a manner consistent with dereverberation.
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Corteza Auditiva , Percepción del Habla , Estimulación Acústica , Adaptación Fisiológica , Animales , Corteza Auditiva/fisiología , Hurones , Humanos , Sonido , Percepción del Habla/fisiologíaRESUMEN
(1) Background: Research has demonstrated that early intervention for children who are hard-of-hearing (CHH) facilitates improved language development. Early speech perception abilities may impact CHH outcomes and guide future intervention. The objective of this study was to examine the use of a conditioned head turn (CHT) task as a measure of speech discrimination in CHH using a clinically feasible protocol. (2) Methods: Speech perception was assessed for a consonant and vowel contrast among 57 CHH and 70 children with normal hearing (CNH) aged 5-17 months using a CHT paradigm. (3) Results: Regardless of hearing status, 74% of CHH and 77% of CNH could discriminate /a-i/, and 55% of CHH and 56% of CNH could discriminate /ba-da/. Regression models revealed that both CHH and CNH performed better on /ba-da/ at 70 dBA compared to 50 dBA. Performance by hearing age showed no speech perception differences for CNH and children with mild hearing loss for either contrast. However, children with hearing losses ≥ 41 dB HL performed significantly poorer than CNH for /a-i/. (4) Conclusions: This study demonstrates the clinical feasibility of assessing early speech perception in infants with hearing loss and replicates previous findings of speech perception abilities among CHH and CNH.
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The speech evoked frequency following response (sFFR) is used to study relationships between neural processing and functional aspects of speech and language that are not captured by click or toneburst evoked auditory brainstem responses (ABR). The sFFR is delayed, deviant, or weak in school age children having a variety of disorders, including autism, dyslexia, reading and language disorders, in relation to their typically developing peers. Much less is known about the developmental characteristics of sFFR, especially in preterm infants, who are at risk of having language delays. In term neonates, phase locking and spectral representation of the fundamental frequency is developed in the early days of life. Spectral representation of higher harmonics and latencies associated with transient portions of the stimulus are still developing in term infants through at least 10 months of age. The goal of this research was to determine whether sFFR could be measured in preterm infants and to characterize its developmental trajectory in the time and frequency domain. Click ABR and sFFR were measured in 28 preterm infants at ages 33 to 64 weeks gestational age. The sFFR could be measured in the majority of infants at 33 weeks gestational age, and the detectability of all sFFR waves was 100% by 64 weeks gestational age. The latency of all waves associated with the transient portion of the response (waves V, A, and O), and most waves (waves D and E) associated with the quasi-steady state decreased with increasing age. The interpeak wave A-O latency did not change with age, indicating that these waves share a neural generator, or the neural generators are developing at the same rate. The spectral amplitude of F0 and the lower frequencies of the first formant increased with age, but that for higher frequencies of the first formant and higher harmonics did not. The results suggest that the sFFR can be reliably recorded in preterm infants, including those cared for in the neonatal intensive care unit. These findings support that in preterm infants, F0 amplitude continues to develop within the first 6 months of life and develops before efficient representation of higher frequency harmonics. Further research is needed to determine if the sFFR in preterm infants is predictive of long-term language or learning disorders.
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Potenciales Evocados Auditivos del Tronco Encefálico , Percepción del Habla , Preescolar , Edad Gestacional , Humanos , Lactante , Recién Nacido , Recien Nacido Prematuro , HablaRESUMEN
Welcome to Current Research in Neurobiology (CRNEUR), the gold open access, sibling journal to Current Opinion in Neurobiology, a journal for timely original research in neuroscience. At its very core, CRNEUR is a journal for creativity and innovation in science and publishing. As a journal, we ambitiously aim for CRNEUR to be a vehicle for what many of us envisioned an academic journal could be. Empowered by our commitment to fairness and transparency-to hold ourselves and others to a higher standard-here we describe our ambitions for innovation going forward. We need your help in this process and welcome your views via this survey (https://www.surveymonkey.co.uk/r/5LHWTML) and on social media (to start or join a discussion please use the hashtag #CRNEUR).
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Primary cortical areas contain maps of sensory features, including sound frequency in primary auditory cortex (A1). Two-photon calcium imaging in mice has confirmed the presence of these global tonotopic maps, while uncovering an unexpected local variability in the stimulus preferences of individual neurons in A1 and other primary regions. Here we show that local heterogeneity of frequency preferences is not unique to rodents. Using two-photon calcium imaging in layers 2/3, we found that local variance in frequency preferences is equivalent in ferrets and mice. Neurons with multipeaked frequency tuning are less spatially organized than those tuned to a single frequency in both species. Furthermore, we show that microelectrode recordings may describe a smoother tonotopic arrangement due to a sampling bias towards neurons with simple frequency tuning. These results help explain previous inconsistencies in cortical topography across species and recording techniques.
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Estimulación Acústica/métodos , Corteza Auditiva/fisiología , Vías Auditivas/fisiología , Percepción Auditiva/fisiología , Mapeo Encefálico/métodos , Animales , Fenómenos Electrofisiológicos/fisiología , Femenino , Hurones , Ratones , Ratones Endogámicos C57BL , Neuronas/fisiologíaRESUMEN
Being able to pick out particular sounds, such as speech, against a background of other sounds represents one of the key tasks performed by the auditory system. Understanding how this happens is important because speech recognition in noise is particularly challenging for older listeners and for people with hearing impairments. Central to this ability is the capacity of neurons to adapt to the statistics of sounds reaching the ears, which helps to generate noise-tolerant representations of sounds in the brain. In more complex auditory scenes, such as a cocktail party - where the background noise comprises other voices, sound features associated with each source have to be grouped together and segregated from those belonging to other sources. This depends on precise temporal coding and modulation of cortical response properties when attending to a particular speaker in a multi-talker environment. Furthermore, the neural processing underlying auditory scene analysis is shaped by experience over multiple timescales.
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OBJECTIVE: Use of personal mobile devices to record patient data appears to be increasing, but remains poorly studied. We sought to determine the extent and reasons that Canadian emergency physicians (EPs) and emergency medicine residents use personal mobile devices to record patient data in the emergency department (ED). METHODS: A national survey was distributed to Canadian EPs and residents between 27/02/17 and 23/03/17. This captured demographics, frequency, and purpose of personal mobile device use to record patient data in the ED. It also asked about obtaining consent, security of information, implications for patient care, and knowledge of relevant regulations. RESULTS: The response rate was 23.1% (406 participants). A third (31.5%) reported using personal mobile devices to record patient data. Most (78.1%) did so more than once a month, and 7.0% did so every shift. Reasons cited included beliefs that using personal mobile devices to record patient data improves care by consultants (36.7%), expedites care (31.3%), and advances medical education (32.8%). Consent was rarely or never documented and a minority of participants (10.9%) indicated they did not obtain consent. More than half of participants (53.2%) reported being unaware of applicable regulations. CONCLUSIONS: This is the first Canadian study on the use of personal mobile devices to record patient data in the ED. Our findings demonstrate current practice may risk privacy breaches. Personal mobile device use to record patient data in the ED is common and Canadian EPs and residents believe that this practice enhances patient care.
OBJECTIF: L'utilisation des appareils mobiles personnels (AMP) pour l'enregistrement de données sur les malades semble de plus en plus fréquente, mais elle a été peu examinée jusqu'à maintenant. Aussi l'étude visait-elle à déterminer l'étendue de la pratique et les raisons pour lesquelles les médecins d'urgence (MU) et les résidents dans le domaine, au Canada, utilisent les AMP pour enregistrer des données sur les malades au service des urgences (SU). MÉTHODE: Un questionnaire d'enquête nationale a été envoyé au MU et aux résidents en la matière, au Canada, entre le 2 février 2017 et le 23 mars 2017. On a ainsi recueilli des données démographiques, de même que des renseignements sur la fréquence de la pratique et les raisons motivant l'utilisation des AMP pour la collecte de données sur les malades au SU. Des questions portaient aussi sur l'obtention du consentement, la sécurité de l'information, la portée de l'acte sur les soins aux malades et la connaissance de la réglementation applicable. RÉSULTATS: Le taux de réponse a atteint 23,1% (406 participants). Un tiers (31,5%) des répondants ont indiqué faire usage d'AMP pour enregistrer des données sur les malades. La plupart (78,1%) les utilisaient plus d'une fois par mois et 7,0%, à toutes les périodes de travail. Les raisons invoquées le plus souvent comprenaient l'opinion selon laquelle l'utilisation des AMP pour l'enregistrement de données sur les malades améliorait les soins par les consultants (36,7%), accélérait la prestation de soins (31,3%) et faisait progresser la formation médicale (32,8%). Le consentement était rarement documenté, voire jamais, et une minorité de répondants (10,9%) ont indiqué ne pas avoir obtenu le consentement des patients. Plus de la moitié des participants (53,2%) ont déclaré ne pas être courant de l'existence de règlements applicables. CONCLUSION: Il s'agit là de la première étude sur l'utilisation des AMP au Canada pour l'enregistrement de données sur les malades au SU. D'après les résultats de l'enquête, la pratique pourrait comporter des risques d'atteinte à la vie privée. L'usage des AMP pour l'enregistrement de données sur les malades au SU est courant, et les MU comme les résidents sont d'avis que la pratique améliore les soins aux malades.
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Documentación/estadística & datos numéricos , Servicio de Urgencia en Hospital , Internado y Residencia , Cuerpo Médico de Hospitales , Teléfono Inteligente/estadística & datos numéricos , Canadá , Humanos , Consentimiento Informado/estadística & datos numéricos , Encuestas y CuestionariosRESUMEN
Pitch perception is critical for recognizing speech, music and animal vocalizations, but its neurobiological basis remains unsettled, in part because of divergent results across species. We investigated whether species-specific differences exist in the cues used to perceive pitch and whether these can be accounted for by differences in the auditory periphery. Ferrets accurately generalized pitch discriminations to untrained stimuli whenever temporal envelope cues were robust in the probe sounds, but not when resolved harmonics were the main available cue. By contrast, human listeners exhibited the opposite pattern of results on an analogous task, consistent with previous studies. Simulated cochlear responses in the two species suggest that differences in the relative salience of the two pitch cues can be attributed to differences in cochlear filter bandwidths. The results support the view that cross-species variation in pitch perception reflects the constraints of estimating a sound's fundamental frequency given species-specific cochlear tuning.
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Cóclea/fisiología , Percepción de la Altura Tonal , Estimulación Acústica , Adolescente , Adulto , Animales , Señales (Psicología) , Femenino , Hurones , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
There are only limited treatments currently available for Motor Neurone Disease, each with modest benefits. However, there is a large amount of research and drug discovery currently underway worldwide. The New Zealand Motor Neurone Disease Registry was established in 2017 to facilitate participation in research and clinical trials, and to aid researchers in planning and recruitment. The NZ MND Registry is an opt in patient registry which collects demographic, contact and clinical data for those who choose to enrol. We report anonymised aggregated data from the first year's enrolment. 12th July 2018, there were 142 participants enrolled in the NZ MND Registry. Participant sex distribution reflects the demographics reported worldwide, but ethnicity is divergent from what is seen in New Zealand overall, with an over-representation of people who identify as New Zealand European. 85.5% of participants are diagnosed with sporadic MND and 6.1% with familial MND. The remainder were participants who have not been diagnosed but have a family history, or positive genetic test for a MND-causing mutation. Levels of disability are reported using ALSFRS-R scores, and show that the majority of participants are within the higher range of the scale. The registry has facilitated entry of patients into three studies to date. The establishment of the NZ MND Registry illustrates a swift launch of a rare disease patient registry. The role of patient registries is an ever changing one, but with clear utility at every point of along the pathway to drug discovery.
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Enfermedad de la Neurona Motora , Sistema de Registros , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedad de la Neurona Motora/epidemiología , Nueva Zelanda/epidemiologíaRESUMEN
BACKGROUND: People carrying out clean intermittent self-catheterisation (CISC) to empty their bladder often suffer repeated urinary tract infections (UTIs). Continuous once-daily, low-dose antibiotic treatment (antibiotic prophylaxis) is commonly advised but knowledge of its effectiveness is lacking. OBJECTIVE: To assess the benefit, harms and cost-effectiveness of antibiotic prophylaxis to prevent UTIs in people who perform CISC. DESIGN: Parallel-group, open-label, patient-randomised 12-month trial of allocated intervention with 3-monthly follow-up. Outcome assessors were blind to allocation. SETTING: UK NHS, with recruitment of patients from 51 sites. PARTICIPANTS: Four hundred and four adults performing CISC and predicted to continue for ≥ 12 months who had suffered at least two UTIs in the previous year or had been hospitalised for a UTI in the previous year. INTERVENTIONS: A central randomisation system using random block allocation set by an independent statistician allocated participants to the experimental group [once-daily oral antibiotic prophylaxis using either 50 mg of nitrofurantoin, 100 mg of trimethoprim (Kent Pharmaceuticals, Ashford, UK) or 250 mg of cefalexin (Sandoz Ltd, Holzkirchen, Germany); n = 203] or the control group of no prophylaxis (n = 201), both for 12 months. MAIN OUTCOME MEASURES: The primary clinical outcome was relative frequency of symptomatic, antibiotic-treated UTI. Cost-effectiveness was assessed by cost per UTI avoided. The secondary measures were microbiologically proven UTI, antimicrobial resistance, health status and participants' attitudes to antibiotic use. RESULTS: The frequency of symptomatic antibiotic-treated UTI was reduced by 48% using prophylaxis [incidence rate ratio (IRR) 0.52, 95% confidence interval (CI) 0.44 to 0.61; n = 361]. Reduction in microbiologically proven UTI was similar (IRR 0.49, 95% CI 0.39 to 0.60; n = 361). Absolute reduction in UTI episodes over 12 months was from a median (interquartile range) of 2 (1-4) in the no-prophylaxis group (n = 180) to 1 (0-2) in the prophylaxis group (n = 181). The results were unchanged by adjustment for days at risk of UTI and the presence of factors giving higher risk of UTI. Development of antimicrobial resistance was seen more frequently in pathogens isolated from urine and Escherichia coli from perianal swabs in participants allocated to antibiotic prophylaxis. The use of prophylaxis incurred an extra cost of £99 to prevent one UTI (not including costs related to increased antimicrobial resistance). The emotional and practical burden of CISC and UTI influenced well-being, but health status measured over 12 months was similar between groups and did not deteriorate significantly during UTI. Participants were generally unconcerned about using antibiotics, including the possible development of antimicrobial resistance. LIMITATIONS: Lack of blinding may have led participants in each group to use different thresholds to trigger reporting and treatment-seeking for UTI. CONCLUSIONS: The results of this large randomised trial, conducted in accordance with best practice, demonstrate clear benefit for antibiotic prophylaxis in terms of reducing the frequency of UTI for people carrying out CISC. Antibiotic prophylaxis use appears safe for individuals over 12 months, but the emergence of resistant urinary pathogens may prejudice longer-term management of recurrent UTI and is a public health concern. Future work includes longer-term studies of antimicrobial resistance and studies of non-antibiotic preventative strategies. TRIAL REGISTRATION: Current Controlled Trials ISRCTN67145101 and EudraCT 2013-002556-32. FUNDING: This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in Health Technology Assessment Vol. 22, No. 24. See the NIHR Journals Library website for further project information.
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Profilaxis Antibiótica/economía , Profilaxis Antibiótica/métodos , Cateterismo Urinario/métodos , Infecciones Urinarias/prevención & control , Adulto , Anciano , Anciano de 80 o más Años , Profilaxis Antibiótica/efectos adversos , Bacteriuria/epidemiología , Análisis Costo-Beneficio , Femenino , Gastos en Salud , Estado de Salud , Humanos , Masculino , Persona de Mediana Edad , Modelos Econométricos , Nitrofurantoína/economía , Nitrofurantoína/uso terapéutico , Satisfacción del Paciente , Calidad de Vida , Años de Vida Ajustados por Calidad de Vida , Autocuidado , Método Simple Ciego , Medicina Estatal , Trimetoprim/economía , Trimetoprim/uso terapéutico , Reino Unido , Infecciones Urinarias/microbiologíaRESUMEN
BACKGROUND: Recurrent urinary tract infections are a commonly reported problem in people who use clean intermittent self-catheterisation. Yet there is a lack of knowledge regarding both the impact on people's lives, the use of prophylactic anti-biotics and perceptions of patients on their use. AIMS: To explore the views and experiences of adults who use clean intermittent self-catheterisation for long-term bladder conditions, with a focus on urinary tract infection experience and prophylactic antibiotic use. DESIGN: A qualitative descriptive study. METHODS: Twenty-six semi-structured qualitative interviews were conducted with individuals recruited from the ANTIC Trial (Antibiotic treatment for intermittent bladder catheterisation: A randomised controlled trial of once daily prophylaxis). Participants were intermittent self-catheter users aged 18 years or older. Interviews took place between August 2015 and January 2016. Transcript data were analysed thematically. FINDINGS: Three overarching topics were revealed with corresponding themes: the experiences of intermittent self-catheterisation and urinary tract infections (normalisation, perceived burden); attitudes towards antibiotics for urinary tract infection treatment (nonchalant attitudes, ambivalence towards antibiotic resistance); and experiences of low-dose prophylaxis antibiotics (habitual behaviour and supportive accountability). CONCLUSION: The emotional and practical burden of catheter use and urinary tract infection was considerable. Beliefs pertaining to antibiotic use were based on utility, gravity of need and perceived efficacy. These opinions were often influenced by clinician recommendations.
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Profilaxis Antibiótica , Autocuidado , Cateterismo Urinario/métodos , Infecciones Urinarias/prevención & control , Adulto , Anciano , Anciano de 80 o más Años , Concienciación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Investigación Cualitativa , Cateterismo Urinario/psicologíaRESUMEN
Despite decades of microelectrode recordings, fundamental questions remain about how auditory cortex represents sound-source location. Here, we used in vivo 2-photon calcium imaging to measure the sensitivity of layer II/III neurons in mouse primary auditory cortex (A1) to interaural level differences (ILDs), the principal spatial cue in this species. Although most ILD-sensitive neurons preferred ILDs favoring the contralateral ear, neurons with either midline or ipsilateral preferences were also present. An opponent-channel decoder accurately classified ILDs using the difference in responses between populations of neurons that preferred contralateral-ear-greater and ipsilateral-ear-greater stimuli. We also examined the spatial organization of binaural tuning properties across the imaged neurons with unprecedented resolution. Neurons driven exclusively by contralateral ear stimuli or by binaural stimulation occasionally formed local clusters, but their binaural categories and ILD preferences were not spatially organized on a more global scale. In contrast, the sound frequency preferences of most neurons within local cortical regions fell within a restricted frequency range, and a tonotopic gradient was observed across the cortical surface of individual mice. These results indicate that the representation of ILDs in mouse A1 is comparable to that of most other mammalian species, and appears to lack systematic or consistent spatial order.
Asunto(s)
Corteza Auditiva/metabolismo , Calcio/metabolismo , Neuronas/metabolismo , Localización de Sonidos/fisiología , Estimulación Acústica/métodos , Potenciales de Acción/fisiología , Animales , Vías Auditivas/metabolismo , Señalización del Calcio/fisiología , Oído/fisiología , Femenino , Lateralidad Funcional/fisiología , Ratones Endogámicos C57BL , Ratones Transgénicos , Procesamiento de Señales Asistido por Computador , Imagen de Colorante Sensible al VoltajeRESUMEN
Although the functionality of the lens water channels aquaporin 1 (AQP1; epithelium) and AQP0 (fiber cells) is well established, less is known about the role of AQP5 in the lens. Since in other tissues AQP5 functions as a regulated water channel with a water permeability (PH2O) some 20 times higher than AQP0, AQP5 could function to modulate PH2O in lens fiber cells. To test this possibility, a fluorescence dye dilution assay was used to calculate the relative PH2O of epithelial cells and fiber membrane vesicles isolated from either the mouse or rat lens, in the absence and presence of HgCl2, an inhibitor of AQP1 and AQP5. Immunolabeling of lens sections and fiber membrane vesicles from mouse and rat lenses revealed differences in the subcellular distributions of AQP5 in the outer cortex between species, with AQP5 being predominantly membranous in the mouse but predominantly cytoplasmic in the rat. In contrast, AQP0 labeling was always membranous in both species. This species-specific heterogeneity in AQP5 membrane localization was mirrored in measurements of PH2O, with only fiber membrane vesicles isolated from the mouse lens, exhibiting a significant Hg2+-sensitive contribution to PH2O. When rat lenses were first organ cultured, immunolabeling revealed an insertion of AQP5 into cortical fiber cells, and a significant increase in Hg2+-sensitive PH2O was detected in membrane vesicles. Our results show that AQP5 forms functional water channels in the rodent lens, and they suggest that dynamic membrane insertion of AQP5 may regulate water fluxes in the lens by modulating PH2O in the outer cortex.