A retrospective study of cases of canine demodicosis submitted to a commercial diagnostic laboratory servicing the United Kingdom and Ireland (2017-2018) part 2; Aerobic culture and antimicrobial susceptibility results.

Clinical diagnostic reports from 508 cases of canine demodicosis diagnosed either by histological or skin scraping analysis from a United Kingdom Accreditation Service (UKAS) accredited veterinary diagnostic laboratory servicing the United Kingdom (UK) and Ireland were evaluated. Of the 508 cases, 284 had skin swabs submitted for culture on the same day the skin biopsy and/or skin scraping were obtained. Dogs with juvenile-onset (JO) demodicosis represented 57.4% of these cases, whilst adult-onset (AO) cases comprised 42.6%. The data revealed that overgrowth of pathogenic bacteria was more common in AO demodicosis cases (75.2%) in comparison to the JO cases (57%). Adult-onset cases also had increased involvement of bacteria belonging to multiple genera and/or yeast (28.9%) in comparison to JO cases (18.4%). Pruritus was significantly associated with an overgrowth of Staphylococcus pseudintermedius (p < 0.001). Resistance to one or more antimicrobial classes was noted in S. pseudintermedius isolates from 56.3% of JO cases with 10.3% of these cases being classified as Multi-Drug Resistant (MDR). Similarly, 51.9% of S. pseudintermedius isolates from the AO cases were noted to be resistant to one or more antimicrobial class with 8.6% of these cases being considered MDR. Cephalosporins were the most frequently administered antimicrobial class noted in submission histories, followed by the penicillin and fluoroquinolone classes. Whilst our findings reveal a high prevalence of concurrent overgrowth of pathogenic bacteria warranting therapeutic intervention in canine demodicosis, the presence of resistance within isolates highlights the need for prudent selection and targeted use of antimicrobial therapy that encompass the key principles of antimicrobial stewardship.

A retrospective study of cases of canine demodicosis submitted to a commercial diagnostic laboratory servicing the United Kingdom and Ireland (2017-2018): Part 1 - Signalment, lesion distribution, treatments, and concurrent diseases.

Canine demodicosis, due to an overpopulation of Demodex spp. mites, remains one of the most common dermatological diseases encountered in small animal practice. The aims of this study were to interrogate submitted histories and diagnostic report results from a large cohort of dogs (n = 508) diagnosed with demodicosis either through histological analysis or the finding of Demodex spp. mites on skin scrapings by a UKAS accredited commercial laboratory servicing the United Kingdom (UK) and Ireland in the years 2017 and 2018. The main findings revealed that short-coated breeds were more likely to develop juvenile-onset (JO) demodicosis, whereas medium- and long-coated breeds were more likely to develop adult-onset (AO) disease. Pododemodicosis was reported more commonly in adult, long-coated breeds. Skin scrapings were positive in only 83.3% of samples that had a corresponding positive biopsy result; this finding highlights the necessity to perform further diagnostic tests if demodicosis remains clinically suspected despite a negative skin scraping result. Concurrent underlying diseases, potentially associated with immunosuppression, were reported in 42/221 (19%) of dogs with AO demodicosis. Serum allergy and Sarcoptes ELISA assays were positive in individual animals in both the JO and AO groups; the clinical significance of these latter findings requires careful interpretation in dogs with confirmed demodicosis.

Temporal, Spatial, and Genomic Analyses of Enterobacteriaceae Clinical Antimicrobial Resistance in Companion Animals Reveals Phenotypes and Genotypes of One Health Concern.

BACKGROUND: Antimicrobial resistance (AMR) is a globally important one health threat. The impact of resistant infections on companion animals, and the potential public health implications of such infections, has not been widely explored, largely due to an absence of structured population-level data. OBJECTIVES: We aimed to efficiently capture and repurpose antimicrobial susceptibility test (AST) results data from several veterinary diagnostic laboratories (VDLs) across the United Kingdom to facilitate national companion animal clinical AMR surveillance. We also sought to harness and genotypically characterize isolates of potential AMR importance from these laboratories. METHODS: We summarized AST results for 29,330 canine and 8,279 feline Enterobacteriaceae isolates originating from companion animal clinical practice, performed between April 2016 and July 2018 from four VDLs, with submissions from 2,237 United Kingdom veterinary practice sites. RESULTS: Escherichia coli (E. coli) was the most commonly isolated Enterobacteriaceae in dogs (69.4% of AST results, 95% confidence interval, CI, 68.7-70.0) and cats (90.5%, CI 89.8-91.3). Multi-drug resistance was reported in 14.1% (CI 13.5-14.8) of canine and 12.0% (CI 11.1-12.9) of feline E. coli isolates. Referral practices were associated with increased E. coli 3rd generation ≤ cephalosporin resistance odds (dogs: odds ratio 2.0, CI 1.2-3.4). We selected 95 E. coli isolates for whole genome analyses, of which seven belonged to sequence type 131, also carrying the plasmid-associated extended spectrum ß-lactamase gene bla CTX-M- 15. The plasmid-mediated colistin resistance gene mcr-9 was also identified for the first time in companion animals. CONCLUSIONS: Linking clinical AMR data with genotypic characterization represents an efficient means of identifying important resistance trends in companion animals on a national scale.

SARS-CoV-2 neutralising antibodies in dogs and cats in the United Kingdom.

Companion animals are susceptible to SARS-CoV-2 infection and sporadic cases of pet infections have occurred in the United Kingdom. Here we present the first large-scale serological survey of SARS-CoV-2 neutralising antibodies in dogs and cats in the UK. Results are reported for 688 sera (454 canine, 234 feline) collected by a large veterinary diagnostic laboratory for routine haematology during three time periods; pre-COVID-19 (January 2020), during the first wave of UK human infections (April-May 2020) and during the second wave of UK human infections (September 2020-February 2021). Both pre-COVID-19 sera and those from the first wave tested negative. However, in sera collected during the second wave, 1.4% (n â€‹= â€‹4) of dogs and 2.2% (n â€‹= â€‹2) of cats tested positive for neutralising antibodies. The low numbers of animals testing positive suggests pet animals are unlikely to be a major reservoir for human infection in the UK. However, continued surveillance of in-contact susceptible animals should be performed as part of ongoing population health surveillance initiatives.

SARS-CoV-2 neutralising antibodies in Dogs and Cats in the United Kingdom.

Companion animals are susceptible to SARS-CoV-2 infection and sporadic cases of pet infections have occurred in the United Kingdom. Here we present the first large-scale serological survey of SARS-CoV-2 neutralising antibodies in dogs and cats in the UK. Results are reported for 688 sera (454 canine, 234 feline) collected by a large veterinary diagnostic laboratory for routine haematology during three time periods; pre-COVID-19 (January 2020), during the first wave of UK human infections (April-May 2020) and during the second wave of UK human infections (September 2020-February 2021). Both pre-COVID-19 sera and those from the first wave tested negative. However, in sera collected during the second wave, 1.4% (n=4) of dogs and 2.2% (n=2) cats tested positive for neutralising antibodies. The low numbers of animals testing positive suggests pet animals are unlikely to be a major reservoir for human infection in the UK. However, continued surveillance of in-contact susceptible animals should be performed as part of ongoing population health surveillance initiatives.

A virtual biobank for companion animals: A parvovirus pilot study.

BACKGROUND: There is a lack of national population data concerning infectious disease in companion animals. Here, we piloted the feasibility of linking diagnostic laboratories, population surveillance and modern sequencing approaches to extract targeted diagnostic samples from laboratories before they were discarded, as a novel route to better understand national epidemiology of major small animal pathogens. METHODS: Samples tested for canine or feline parvovirus were requested from a national veterinary diagnostic laboratory and analysed by Sanger or next generation sequencing. Samples were linked to electronic health data held in the SAVSNET database. RESULTS: Sequences obtained from positive samples, together with associated metadata, provided new insights into the recent geographical distribution of parvovirus strains in circulation in the United Kingdom (UK). CONCLUSIONS: This collaboration with industry represents a 'National Virtual Biobank' that can rapidly be called on, to efficiently add new layers of epidemiological information of relevance to animal, and potentially human, population health.

Total remission or persistence of tinnitus and decreased sound level tolerance in adolescents with normal audiograms: A follow-up study.

BACKGROUND: Tinnitus may reflect hidden cochlear synaptic injury that does not express in the audiogram, but leads to neuroplastic changes in auditory pathways that, in turn, reduce tolerance to sounds. Such injury may follow the exposure to loud sounds. The aim of this study was to follow-up adolescents enrolled in a private school to evaluate the prevalence of tinnitus and reduced sound level tolerance (SLT) with 1-year interval, as well as to observe rates of tinnitus persistence, remission and incidence of new cases by repeat measurements. METHODS: In Study 1 (Sanchez et al., 2016), we evaluated 170 adolescents by a questionnaire about tinnitus and reduced tolerance to ordinary sounds and by measurements in a sound booth: audiometry (0.25-16kHz), Loudness Discomfort Levels (LDL, 0.5-4kHz) and tinnitus pitch/loudness matching (if present). Tinnitus measured in the booth was then called "confirmed tinnitus." In Study 2, we revaluated 54 adolescents who returned voluntarily 1 year later to repeat all measurements. RESULTS: From Study 1 to 2, the prevalence of confirmed tinnitus reduced from 28.8% (49/170) to 14.9% (8/54) in retested subjects, which includes the cases of persisting tinnitus (confirmed tinnitus in both studies, n=6/54=11.2%) and the new cases of tinnitus (confirmed tinnitus just at Study 2, n=2/54=3.7%). Among the 15 adolescents with confirmed tinnitus at Study 1 who returned for Study 2, 40% had persistent tinnitus (n=6) and 60% did not (remitted tinnitus, n=9). SLT was reduced by 17.3dB in cases with persistent tinnitus (P<0.0002), similar to the findings of Study 1, and returned to normal levels in subjects with remitted tinnitus. Hearing thresholds averaged 4.37dBHL and were <20dBHL in 97% of ears and all frequencies. At 14 and 16kHz thresholds were bilaterally elevated at Study 1 (5.07dB) and 2 (5.56dB) in adolescents with confirmed tinnitus. CONCLUSIONS: Tinnitus and reduced sound tolerance could feature early signals of hidden synaptic injury that is prevalent among adolescents and hidden from the audiogram. The strong relationship between both symptoms, in addition to low-level increases in hearing thresholds at high frequencies in the extended audiogram, poses a challenge for future hearing health and should be further evaluated as a possible intrinsic vulnerability for lesions following exposure to loud sounds. Moreover, the relationship between their spontaneous remissions may signal a possible synaptic repair, which has been reported in animal models.

DIVERSITY OF STAPHYLOCOCCAL SPECIES CULTURED FROM CAPTIVE LIVINGSTONE'S FRUIT BATS (PTEROPUS LIVINGSTONII) AND THEIR ENVIRONMENT.

Livingstone's fruit bats (Pteropus livingstonii) are critically endangered and a captive population has been established as part of the International Union for Conservation of Nature Species Action Plan. The largest colony, in Jersey Zoo, was sampled for staphylococcal carriage and at infection sites, as disease associated with staphylococci had previously been found. Staphylococci were cultured from swabs from 44 bats (skin, oropharynx, mouth ejecta, skin lesions) and from their enclosure. The isolates were identified by matrix-assisted laser desorption-ionization time of flight mass spectrometry; antimicrobial susceptibility testing was performed by disc diffusion and screening for mecA and mecC. Seventeen species of coagulase-negative staphylococci including Staphylococcus xylosus, S. kloosii, S. nepalensis, and S. simiae were isolated. Staphylococcus aureus was identified from both carriage and lesional sites. These findings suggest S. nepalensis may be part of the normal carriage flora of bats. Antimicrobial resistance rates were low and methicillin-resistant Staphylococcus aureus (MRSA) was not identified. Sampling of mouth ejecta for staphylococci may provide results representative for carriage sites.

Comparison of Tinnitus Loudness Measures: Matching, Rating, and Scaling.

Purpose Chronic tinnitus ("ringing in the ears") is a phantom auditory perception with no cure. A goal of treatment is often to reduce the loudness of tinnitus. However, tinnitus loudness cannot be measured objectively. It is most commonly assessed by obtaining a loudness match (LM) with a pure tone and by using a numeric rating scale (NRS). Constrained loudness scaling (CLS) is a more recent measure of tinnitus loudness that utilizes auditory training of a fixed loudness scale to guide tinnitus loudness judgments. The purpose of this study was to compare results using these 3 measures of tinnitus loudness. Method This study obtained tinnitus loudness measures of LM, NRS, and CLS with 170 participants. These participants are part of a larger study obtaining repeated measures over 6 months. Only baseline data are presented. Results Correlations between all measures were weak to moderate: LM versus CLS ( r = .46), CLS versus NRS ( r = .49), and LM versus NRS ( r = .38). Conclusion Further systematic research is needed to more fully understand the relationships between these different measures and to establish a valid measure of tinnitus loudness.

Envelope following responses, noise exposure, and evidence of cochlear synaptopathy in humans: Correction and comment.

A correction and comment are provided for a recent article by Paul, Waheed, Bruce, and Roberts [(2017). J. Acoust. Soc. Am. 142(5), EL434-EL440].

Auditory-somatosensory bimodal stimulation desynchronizes brain circuitry to reduce tinnitus in guinea pigs and humans.

The dorsal cochlear nucleus is the first site of multisensory convergence in mammalian auditory pathways. Principal output neurons, the fusiform cells, integrate auditory nerve inputs from the cochlea with somatosensory inputs from the head and neck. In previous work, we developed a guinea pig model of tinnitus induced by noise exposure and showed that the fusiform cells in these animals exhibited increased spontaneous activity and cross-unit synchrony, which are physiological correlates of tinnitus. We delivered repeated bimodal auditory-somatosensory stimulation to the dorsal cochlear nucleus of guinea pigs with tinnitus, choosing a stimulus interval known to induce long-term depression (LTD). Twenty minutes per day of LTD-inducing bimodal (but not unimodal) stimulation reduced physiological and behavioral evidence of tinnitus in the guinea pigs after 25 days. Next, we applied the same bimodal treatment to 20 human subjects with tinnitus using a double-blinded, sham-controlled, crossover study. Twenty-eight days of LTD-inducing bimodal stimulation reduced tinnitus loudness and intrusiveness. Unimodal auditory stimulation did not deliver either benefit. Bimodal auditory-somatosensory stimulation that induces LTD in the dorsal cochlear nucleus may hold promise for suppressing chronic tinnitus, which reduces quality of life for millions of tinnitus sufferers worldwide.

Subcortical amplitude modulation encoding deficits suggest evidence of cochlear synaptopathy in normal-hearing 18-19 year olds with higher lifetime noise exposure.

Noise exposure and aging can damage cochlear synapses required for suprathreshold listening, even when cochlear structures needed for hearing at threshold remain unaffected. To control for effects of aging, behavioral amplitude modulation (AM) detection and subcortical envelope following responses (EFRs) to AM tones in 25 age-restricted (18-19 years) participants with normal thresholds, but different self-reported noise exposure histories were studied. Participants with more noise exposure had smaller EFRs and tended to have poorer AM detection than less-exposed individuals. Simulations of the EFR using a well-established cochlear model were consistent with more synaptopathy in participants reporting greater noise exposure.

Evidence that hidden hearing loss underlies amplitude modulation encoding deficits in individuals with and without tinnitus.

Damage to auditory nerve fibers that expresses with suprathreshold sounds but is hidden from the audiogram has been proposed to underlie deficits in temporal coding ability observed among individuals with otherwise normal hearing, and to be present in individuals experiencing chronic tinnitus with clinically normal audiograms. We tested whether these individuals may have hidden synaptic losses on auditory nerve fibers with low spontaneous rates of firing (low-SR fibers) that are important for coding suprathreshold sounds in noise while high-SR fibers determining threshold responses in quiet remain relatively unaffected. Tinnitus and control subjects were required to detect the presence of amplitude modulation (AM) in a 5 kHz, suprathreshold tone (a frequency in the tinnitus frequency region of the tinnitus subjects, whose audiometric thresholds were normal to 12 kHz). The AM tone was embedded within background noise intended to degrade the contribution of high-SR fibers, such that AM coding was preferentially reliant on low-SR fibers. We also recorded by electroencephalography the "envelope following response" (EFR, generated in the auditory midbrain) to a 5 kHz, 85 Hz AM tone presented in the same background noise, and also in quiet (both low-SR and high-SR fibers contributing to AM coding in the latter condition). Control subjects with EFRs that were comparatively resistant to the addition of background noise had better AM detection thresholds than controls whose EFRs were more affected by noise. Simulated auditory nerve responses to our stimulus conditions using a well-established peripheral model suggested that low-SR fibers were better preserved in the former cases. Tinnitus subjects had worse AM detection thresholds and reduced EFRs overall compared to controls. Simulated auditory nerve responses found that in addition to severe low-SR fiber loss, a degree of high-SR fiber loss that would not be expected to affect audiometric thresholds was needed to explain the results in tinnitus subjects. The results indicate that hidden hearing loss could be sufficient to account for impaired temporal coding in individuals with normal audiograms as well as for cases of tinnitus without audiometric hearing loss.

Tinnitus is associated with reduced sound level tolerance in adolescents with normal audiograms and otoacoustic emissions.

Recent neuroscience research suggests that tinnitus may reflect synaptic loss in the cochlea that does not express in the audiogram but leads to neural changes in auditory pathways that reduce sound level tolerance (SLT). Adolescents (N = 170) completed a questionnaire addressing their prior experience with tinnitus, potentially risky listening habits, and sensitivity to ordinary sounds, followed by psychoacoustic measurements in a sound booth. Among all adolescents 54.7% reported by questionnaire that they had previously experienced tinnitus, while 28.8% heard tinnitus in the booth. Psychoacoustic properties of tinnitus measured in the sound booth corresponded with those of chronic adult tinnitus sufferers. Neither hearing thresholds (≤15 dB HL to 16 kHz) nor otoacoustic emissions discriminated between adolescents reporting or not reporting tinnitus in the sound booth, but loudness discomfort levels (a psychoacoustic measure of SLT) did so, averaging 11.3 dB lower in adolescents experiencing tinnitus in the acoustic chamber. Although risky listening habits were near universal, the teenagers experiencing tinnitus and reduced SLT tended to be more protective of their hearing. Tinnitus and reduced SLT could be early indications of a vulnerability to hidden synaptic injury that is prevalent among adolescents and expressed following exposure to high level environmental sounds.

Maladaptive plasticity in tinnitus--triggers, mechanisms and treatment.

Tinnitus is a phantom auditory sensation that reduces quality of life for millions of people worldwide, and for which there is no medical cure. Most cases of tinnitus are associated with hearing loss caused by ageing or noise exposure. Exposure to loud recreational sound is common among the young, and this group are at increasing risk of developing tinnitus. Head or neck injuries can also trigger the development of tinnitus, as altered somatosensory input can affect auditory pathways and lead to tinnitus or modulate its intensity. Emotional and attentional state could be involved in the development and maintenance of tinnitus via top-down mechanisms. Thus, military personnel in combat are particularly at risk owing to combined risk factors (hearing loss, somatosensory system disturbances and emotional stress). Animal model studies have identified tinnitus-associated neural changes that commence at the cochlear nucleus and extend to the auditory cortex and other brain regions. Maladaptive neural plasticity seems to underlie these changes: it results in increased spontaneous firing rates and synchrony among neurons in central auditory structures, possibly generating the phantom percept. This Review highlights the links between animal and human studies, and discusses several therapeutic approaches that have been developed to target the neuroplastic changes underlying tinnitus.

Achieving across-laboratory replicability in psychophysical scaling.

It is well known that, although psychophysical scaling produces good qualitative agreement between experiments, precise quantitative agreement between experimental results, such as that routinely achieved in physics or biology, is rarely or never attained. A particularly galling example of this is the fact that power function exponents for the same psychological continuum, measured in different laboratories but ostensibly using the same scaling method, magnitude estimation, can vary by a factor of three. Constrained scaling (CS), in which observers first learn a standardized meaning for a set of numerical responses relative to a standard sensory continuum and then make magnitude judgments of other sensations using the learned response scale, has produced excellent quantitative agreement between individual observers' psychophysical functions. Theoretically it could do the same for across-laboratory comparisons, although this needs to be tested directly. We compared nine different experiments from four different laboratories as an example of the level of across experiment and across-laboratory agreement achievable using CS. In general, we found across experiment and across-laboratory agreement using CS to be significantly superior to that typically obtained with conventional magnitude estimation techniques, although some of its potential remains to be realized.

Evidence for differential modulation of primary and nonprimary auditory cortex by forward masking in tinnitus.

It has been proposed that tinnitus is generated by aberrant neural activity that develops among neurons in tonotopic of regions of primary auditory cortex (A1) affected by hearing loss, which is also the frequency region where tinnitus percepts localize (Eggermont and Roberts 2004; Roberts et al., 2010, 2013). These models suggest (1) that differences between tinnitus and control groups of similar age and audiometric function should depend on whether A1 is probed in tinnitus frequency region (TFR) or below it, and (2) that brain responses evoked from A1 should track changes in the tinnitus percept when residual inhibition (RI) is induced by forward masking. We tested these predictions by measuring (128-channel EEG) the sound-evoked 40-Hz auditory steady-state response (ASSR) known to localize tonotopically to neural sources in A1. For comparison the N1 transient response localizing to distributed neural sources in nonprimary cortex (A2) was also studied. When tested under baseline conditions where tinnitus subjects would have heard their tinnitus, ASSR responses were larger in a tinnitus group than in controls when evoked by 500 Hz probes while the reverse was true for tinnitus and control groups tested with 5 kHz probes, confirming frequency-dependent group differences in this measure. On subsequent trials where RI was induced by masking (narrow band noise centered at 5 kHz), ASSR amplitude increased in the tinnitus group probed at 5 kHz but not in the tinnitus group probed at 500 Hz. When collapsed into a single sample tinnitus subjects reporting comparatively greater RI depth and duration showed comparatively larger ASSR increases after masking regardless of probe frequency. Effects of masking on ASSR amplitude in the control groups were completely reversed from those in the tinnitus groups, with no change seen to 5 kHz probes but ASSR increases to 500 Hz probes even though the masking sound contained no energy at 500 Hz (an "off-frequency" masking effect). In contrast to these findings for the ASSR, N1 amplitude was larger in tinnitus than control groups at both probe frequencies under baseline conditions, decreased after masking in all conditions, and did not relate to RI. These results suggest that aberrant neural activity occurring in the TFR of A1 underlies tinnitus and its modulation during RI. They indicate further that while neural changes occur in A2 in tinnitus, these changes do not reflect the tinnitus percept. Models for tinnitus and forward masking are described that integrate these findings within a common framework.

Tinnitus: animal models and findings in humans.

Chronic tinnitus (ringing of the ears) is a medically untreatable condition that reduces quality of life for millions of individuals worldwide. Most cases are associated with hearing loss that may be detected by the audiogram or by more sensitive measures. Converging evidence from animal models and studies of human tinnitus sufferers indicates that, while cochlear damage is a trigger, most cases of tinnitus are not generated by irritative processes persisting in the cochlea but by changes that take place in central auditory pathways when auditory neurons lose their input from the ear. Forms of neural plasticity underlie these neural changes, which include increased spontaneous activity and neural gain in deafferented central auditory structures, increased synchronous activity in these structures, alterations in the tonotopic organization of auditory cortex, and changes in network behavior in nonauditory brain regions detected by functional imaging of individuals with tinnitus and corroborated by animal investigations. Research on the molecular mechanisms that underlie neural changes in tinnitus is in its infancy and represents a frontier for investigation.

Modulation of electrocortical brain activity by attention in individuals with and without tinnitus.

Age and hearing-level matched tinnitus and control groups were presented with a 40 Hz AM sound using a carrier frequency of either 5 kHz (in the tinnitus frequency region of the tinnitus subjects) or 500 Hz (below this region). On attended blocks subjects pressed a button after each sound indicating whether a single 40 Hz AM pulse of variable increased amplitude (target, probability 0.67) had or had not occurred. On passive blocks subjects rested and ignored the sounds. The amplitude of the 40 Hz auditory steady-state response (ASSR) localizing to primary auditory cortex (A1) increased with attention in control groups probed at 500 Hz and 5 kHz and in the tinnitus group probed at 500 Hz, but not in the tinnitus group probed at 5 kHz (128 channel EEG). N1 amplitude (this response localizing to nonprimary cortex, A2) increased with attention at both sound frequencies in controls but at neither frequency in tinnitus. We suggest that tinnitus-related neural activity occurring in the 5 kHz but not the 500 Hz region of tonotopic A1 disrupted attentional modulation of the 5 kHz ASSR in tinnitus subjects, while tinnitus-related activity in A1 distributing nontonotopically in A2 impaired modulation of N1 at both sound frequencies.