Long-term treatment with aldosterone slows the progression of age-related hearing loss

Publication date: Available online 5 May 2016
Source:Hearing Research
Author(s): Joshua Halonen, Ashley Hinton, Robert D. Frisina, Bo Ding, Xiaoxia Zhu, Joseph P. Walton
Age-related hearing loss (ARHL), clinically referred to as presbycusis, is one of the three most prevalent chronic medical conditions of our elderly, with the majority of persons over the age of 60 suffering from some degree of ARHL. The progressive loss of auditory sensitivity and perceptual capability results in significant declines in workplace productivity, quality of life, cognition and abilities to communicate effectively. Aldosterone is a mineralocorticoid hormone produced in the adrenal glands and plays a role in the maintenance of key ion pumps, including the Na-K+-Cl co-transporter 1 or NKCC1, which is involved in homeostatic maintenance of the endocochlear potential. Previously we reported that aldosterone (1 μM) increases NKCC1 protein expression in vitro and that this up-regulation of NKCC1 was not dose-dependent (dosing range from 1 nM to 100 μM). In the current study we measured behavioral and electrophysiological hearing function in middle-aged mice following long-term systemic treatment with aldosterone. We also confirmed that blood pressure remained stable during treatment and that NKCC1 protein expression was upregulated. Pre-pulse inhibition of the acoustic startle response was used as a functional measure of hearing, and the auditory brainstem response was used as an objective measure of peripheral sensitivity. Long-term treatment with aldosterone improved both behavioral and physiological measures of hearing (ABR thresholds). These results are the first to demonstrate a protective effect of aldosterone on age-related hearing loss and pave the way for translational drug development, using aldosterone as a key component to prevent or slow down the progression of ARHL.



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Time dependent structure of postural sway in individuals with multiple sclerosis

Publication date: July 2016
Source:Gait & Posture, Volume 48
Author(s): Kathleen L. Roeing, Douglas A. Wajda, Jacob J. Sosnoff
Non-linear analyses, which examine the time dependent structure of physiological output have been found to be able to detect subtle differences in postural control between pathological groups and healthy controls while traditional linear parameters do not. This investigation examines whether a specific non-linear metric, approximate entropy, may provide a novel biomarker for balance impairment in individuals with multiple sclerosis (MS) who have normal sway. This analysis included a sample of 30 individuals with MS with normal postural sway and 36 controls. Participants stood on a force platform for two trials of 30s with eyes open. Postural control was indexed by sway area, mean velocity along the antero-posterior (AP) and mediolateral (ML) axis. The time dependent structure of the COP along the AP and ML axes was indexed with approximate entropy (ApEnAP; ApEnML). T-tests and Mann–Whitney U tests were utilized to analyze differences between groups. Per design there were no differences in sway area between the MS and control groups. Additionally, there were no differences in sway velocity. The MS group had lower ApEnML values compared to the control group (U=376, p=.026). The results indicate that individuals with MS who have normal sway area had greater time dependent structure in ML sway. This investigation highlights the utility of non-linear analyses when assessing balance impairment in MS samples that present with minimal sway area.



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Effects of running-induced fatigue on plantar pressure distribution in novice runners with different foot types

Publication date: Available online 5 May 2016
Source:Gait & Posture
Author(s): Mehrdad Anbarian, Hamed Esmaili
This study aimed to assess the effects of running-induced fatigue on plantar pressure parameters in novice runners with low and high medial longitudinal arch. Plantar pressure data from 42 novice runners (21 with high, and 21 with low arch) were collected before and after running-induced fatigue protocol during running at 3.3m/s along the Footscan^® platform. Peak plantar pressure, peak force and force-time integral (impulse) were measured in ten anatomical zones. Relative time for foot roll-over phases and medio-lateral force ratio were calculated before and after the fatigue protocol. After the fatigue protocol, increases in the peak pressure under the first-third metatarsal zones and reduction under the fourth-fifth metatarsal regions were observed in the low arch individuals. In the high arch group, increases in peak pressure under the fourth-fifth metatarsal zones after the running-induced fatigue was observed. It could be concluded that running-induced fatigue had different effects on plantar pressure distribution pattern among novice runners with low and high medial longitudinal foot arch. These findings could provide some information related to several running injuries among individuals with different foot types.



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Long-term treatment with aldosterone slows the progression of age-related hearing loss

Publication date: Available online 5 May 2016
Source:Hearing Research
Author(s): Joshua Halonen, Ashley Hinton, Robert D. Frisina, Bo Ding, Xiaoxia Zhu, Joseph P. Walton
Age-related hearing loss (ARHL), clinically referred to as presbycusis, is one of the three most prevalent chronic medical conditions of our elderly, with the majority of persons over the age of 60 suffering from some degree of ARHL. The progressive loss of auditory sensitivity and perceptual capability results in significant declines in workplace productivity, quality of life, cognition and abilities to communicate effectively. Aldosterone is a mineralocorticoid hormone produced in the adrenal glands and plays a role in the maintenance of key ion pumps, including the Na-K+-Cl co-transporter 1 or NKCC1, which is involved in homeostatic maintenance of the endocochlear potential. Previously we reported that aldosterone (1 μM) increases NKCC1 protein expression in vitro and that this up-regulation of NKCC1 was not dose-dependent (dosing range from 1 nM to 100 μM). In the current study we measured behavioral and electrophysiological hearing function in middle-aged mice following long-term systemic treatment with aldosterone. We also confirmed that blood pressure remained stable during treatment and that NKCC1 protein expression was upregulated. Pre-pulse inhibition of the acoustic startle response was used as a functional measure of hearing, and the auditory brainstem response was used as an objective measure of peripheral sensitivity. Long-term treatment with aldosterone improved both behavioral and physiological measures of hearing (ABR thresholds). These results are the first to demonstrate a protective effect of aldosterone on age-related hearing loss and pave the way for translational drug development, using aldosterone as a key component to prevent or slow down the progression of ARHL.



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Involvement of Ubiquitin-Editing Protein A20 in Modulating Inflammation in Rat Cochlea Associated with Silver Nanoparticle-Induced CD68 Upregulation and TLR4 Activation.

Involvement of Ubiquitin-Editing Protein A20 in Modulating Inflammation in Rat Cochlea Associated with Silver Nanoparticle-Induced CD68 Upregulation and TLR4 Activation.

Nanoscale Res Lett. 2016 Dec;11(1):240

Authors: Feng H, Pyykkö I, Zou J

Abstract
Silver nanoparticles (AgNPs) were shown to temporarily impair the biological barriers in the skin of the external ear canal, mucosa of the middle ear, and inner ear, causing partially reversible hearing loss after delivery into the middle ear. The current study aimed to elucidate the molecular mechanism, emphasizing the TLR signaling pathways in association with the potential recruitment of macrophages in the cochlea and the modulation of inflammation by ubiquitin-editing protein A20. Molecules potentially involved in these signaling pathways were thoroughly analysed using immunohistochemistry in the rat cochlea exposed to AgNPs at various concentrations through intratympanic injection. The results showed that 0.4 % AgNPs but not 0.02 % AgNPs upregulated the expressions of CD68, TLR4, MCP1, A20, and RNF11 in the strial basal cells, spiral ligament fibrocytes, and non-sensory supporting cells of Corti's organ. 0.4 % AgNPs had no effect on CD44, TLR2, MCP2, Rac1, myosin light chain, VCAM1, Erk1/2, JNK, p38, IL-1β, TNF-α, TNFR1, TNFR2, IL-10, or TGF-β. This study suggested that AgNPs might confer macrophage-like functions on the strial basal cells and spiral ligament fibrocytes and enhance the immune activities of non-sensory supporting cells of Corti's organ through the upregulation of CD68, which might be involved in TLR4 activation. A20 and RNF11 played roles in maintaining cochlear homeostasis via negative regulation of the expressions of inflammatory cytokines.

PMID: 27142878 [PubMed]

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Evidence-based guidelines for recommending cochlear implantation for young children: Audiological criteria and optimizing age at implantation.

Evidence-based guidelines for recommending cochlear implantation for young children: Audiological criteria and optimizing age at implantation.

Int J Audiol. 2016 May 4;:1-10

Authors: Leigh JR, Dettman SJ, Dowell RC

Abstract
OBJECTIVE: Establish up-to-date evidence-based guidelines for recommending cochlear implantation for young children.
DESIGN: Speech perception results for early-implanted children were compared to children using traditional amplification. Equivalent pure-tone average (PTA) hearing loss for cochlear implant (CI) users was established. Language of early-implanted children was assessed over six years and compared to hearing peers.
STUDY SAMPLE: Seventy-eight children using CIs and 62 children using traditional amplification with hearing losses ranging 25-120 dB HL PTA (speech perception study). Thirty-two children who received a CI before 2.5 years of age (language study).
RESULTS: Speech perception outcomes suggested that children with a PTA greater than 60 dB HL have a 75% chance of benefit over traditional amplification. More conservative criteria applied to the data suggested that children with PTA greater than 82 dB HL have a 95% chance of benefit. Children implanted under 2.5 years with no significant cognitive deficits made normal language progress but retained a delay approximately equal to their age at implantation.
CONCLUSIONS: Hearing-impaired children under three years of age may benefit from cochlear implantation if their PTA exceeds 60 dB HL bilaterally. Implantation as young as possible should minimize any language delay resulting from an initial period of auditory deprivation.

PMID: 27142630 [PubMed - as supplied by publisher]

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Evidence-based guidelines for recommending cochlear implantation for young children: Audiological criteria and optimizing age at implantation.

Evidence-based guidelines for recommending cochlear implantation for young children: Audiological criteria and optimizing age at implantation.

Int J Audiol. 2016 May 4;:1-10

Authors: Leigh JR, Dettman SJ, Dowell RC

Abstract
OBJECTIVE: Establish up-to-date evidence-based guidelines for recommending cochlear implantation for young children.
DESIGN: Speech perception results for early-implanted children were compared to children using traditional amplification. Equivalent pure-tone average (PTA) hearing loss for cochlear implant (CI) users was established. Language of early-implanted children was assessed over six years and compared to hearing peers.
STUDY SAMPLE: Seventy-eight children using CIs and 62 children using traditional amplification with hearing losses ranging 25-120 dB HL PTA (speech perception study). Thirty-two children who received a CI before 2.5 years of age (language study).
RESULTS: Speech perception outcomes suggested that children with a PTA greater than 60 dB HL have a 75% chance of benefit over traditional amplification. More conservative criteria applied to the data suggested that children with PTA greater than 82 dB HL have a 95% chance of benefit. Children implanted under 2.5 years with no significant cognitive deficits made normal language progress but retained a delay approximately equal to their age at implantation.
CONCLUSIONS: Hearing-impaired children under three years of age may benefit from cochlear implantation if their PTA exceeds 60 dB HL bilaterally. Implantation as young as possible should minimize any language delay resulting from an initial period of auditory deprivation.

PMID: 27142630 [PubMed - as supplied by publisher]

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