Tuesday, November 24, 2020

Unravelling the molecular players at the cholinergic efferent synapse of the zebrafish lateral line.

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Unravelling the molecular players at the cholinergic efferent synapse of the zebrafish lateral line.

J Neurosci. 2020 Nov 16;:

Authors: Carpaneto Freixas AE, Moglie MJ, Castagnola T, Salatino L, Domene S, Marcovich I, Gallino S, Wedemeyer C, Goutman JD, Plazas PV, Elgoyhen AB

Abstract
The lateral line (LL) is a sensory system that allows fish and amphibians to detect water currents. LL responsiveness is modulated by efferent neurons which aid to distinguish between external and self-generated stimuli, maintaining sensitivity to relevant cues. One component of the efferent system is cholinergic, the activation of which inhibits afferent activity. LL hair cells (HC) share structural, functional and molecular similarities with those of the cochlea, making them a popular model for studying human hearing and balance disorders. Due to these commonalities, one could propose that the receptor at the LL efferent synapse is a α9α10 nicotinic cholinergic one (nAChR). However, the identities of the molecular players underlying acetylcholine (ACh)-mediated inhibition in the LL remain unknown. Surprisingly, through the analysis of single-cell expression studies and in situ hybridization, we describe that α9, but not α10 subunits, are enriched in zebrafish HC. Moreov er, the heterologous expression of zebrafish α9 subunits indicates that homomeric receptors are functional and exhibit robust ACh-gated currents blocked by α-Bungarotoxin and strychnine. In addition, in vivo Ca2+ imaging on mechanically-stimulated zebrafish LL HC show that ACh elicits a decrease in evoked Ca2+ signals, irrespective of HC polarity. This effect is blocked by both α-Bungarotoxin and apamin, indicating coupling of ACh-mediated effects to SK potassium channels. Our results indicate that an α9-containing (α9*) nAChR operates at the zebrafish LL efferent synapse. Moreover, the activation of α9* nAChRs most likely leads to LL HC hyperpolarization served by the activation of Ca2+-dependent SK potassium channels.SIGNIFICANCE STATEMENTThe fish lateral line (LL) mechanosensory system shares structural, functional and molecular similarities with those of the mammalian cochlea. Thus, it has become an accessible model for studying human hearing and balance disorders. However , the molecular players serving efferent control of LL hair cell (HC) activity have not been identified. Here we demonstrate that, different to the hearing organ of vertebrate species, a nicotinic acetylcholine receptor composed only of α9 subunits operates at the LL efferent synapse. Activation of α9-containing (α9*) receptors leads to LL HC hyperpolarization due to the opening of Ca2+-dependent potassium SK channels. These results will further aid in the interpretation of data obtained from LL HC as a model for cochlear HC.

PMID: 33203744 [PubMed - as supplied by publisher]

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Protection of Cochlear Ribbon Synapses and Prevention of Hidden Hearing Loss.

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Protection of Cochlear Ribbon Synapses and Prevention of Hidden Hearing Loss.

Neural Plast. 2020;2020:8815990

Authors: Wei M, Wang W, Liu Y, Mao X, Chen TS, Lin P

Abstract
In the auditory system, ribbon synapses are vesicle-associated structures located between inner hair cells (IHCs) and spiral ganglion neurons that are implicated in the modulation of trafficking and fusion of synaptic vesicles at the presynaptic terminals. Synapse loss may result in hearing loss and difficulties with understanding speech in a noisy environment. This phenomenon happens without permanent hearing loss; that is, the cochlear synaptopathy is "hidden." Recent studies have reported that synapse loss might be critical in the pathogenesis of hidden hearing loss. A better understanding of the molecular mechanisms of the formation, structure, regeneration, and protection of ribbon synapses will assist in the design of potential therapeutic strategies. In this review, we describe and summarize the following aspects of ribbon synapses: (1) functional and structural features, (2) potential mechanisms of damage, (3) therapeutic research on protecting the synapses, and (4) t he role of synaptic regeneration in auditory neuropathy and the current options for synapse rehabilitation.

PMID: 33204247 [PubMed - in process]

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AHNS endocrine surgery section consensus statement on nasopharyngolaryngoscopy and clinic reopening during COVID-19: How to get back to optimal safe care.

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AHNS endocrine surgery section consensus statement on nasopharyngolaryngoscopy and clinic reopening during COVID-19: How to get back to optimal safe care.

Head Neck. 2020 Nov 17;:

Authors: Bleier B, Workman A, Burks C, Maxfield A, Stack BC, Nathan CA, McCammon S, Varvares M, Schmalbach C, Wang S, Califano J, Shnayder Y, Gillespie MB, Enepekides D, Witterick I, El-Sayed I, Lin D, Patel U, Kraus D, Randolph G

Abstract
This article provides best practice guidelines regarding nasopharyngolaryngoscopy and OHNS clinic reopening during the COVID-19 pandemic. The aim is to provide evidence-based recommendations defining the risks of COVID-19 in clinic, the importance of pre-visit screening in addition to testing, along with ways to adhere to CDC guidelines for environmental, source, and engineering controls.

PMID: 33205536 [PubMed - as supplied by publisher]

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Peroral Endoscopic Myotomy for Esophageal Motility Disorders.

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Peroral Endoscopic Myotomy for Esophageal Motility Disorders.

Clin Endosc. 2020 Nov 20;:

Authors: Kim JY, Min YW

Abstract
Peroral endoscopic myotomy (POEM) is one of the most clinically successful tunnel-based minimally invasive endoscopic treatments. The classic indications of POEM include achalasia of all types, including failed prior treatments, and expanded indications include the non-achalasia esophageal motility disorders, such as esophagogastric junction outflow obstruction, diffuse esophageal spasm, and jackhammer esophagus. For achalasia treatment, POEM has achieved a comparable surgical efficacy and a safety outcome and, therefore, has emerged as a first-line treatment. For non-achalasia esophageal motility disorders, POEM has also shown high clinical response rates. The complication rate of POEM for esophageal motility disorders is low and most complications are managed with conservative treatment. Currently, POEM is a representative procedure of natural orifice transluminal endoscopic surgery, which has shown a good clinical efficacy with low complication rates for esophageal motilit y disorders including achalasia. However, further studies are needed to treat non-achalasia motility disorder via POEM.

PMID: 33212547 [PubMed - as supplied by publisher]

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Genetic Mutations in Young Nonsmoking Patients With Oral Cavity Cancer: A Systematic Review.

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Genetic Mutations in Young Nonsmoking Patients With Oral Cavity Cancer: A Systematic Review.

OTO Open. 2020 Oct-Dec;4(4):2473974X20970181

Authors: Bahethi RR, Stepan KO, Pinotti R, Li R, Agrawal N, Puram SV, Miles BA, Barber B

Abstract
Objective: This investigation aims to review the known genetic mutations associated with oral cavity squamous cell carcinoma (OCSCC) in young adults with limited environmental risk factors (YLERs).
Data Sources: A comprehensive search strategy was designed to identify studies in MEDLINE (Ovid), Embase (Ovid), and Scopus from database inception to May 2017 that included adults ≤50 years of age with OCSCC and minimal tobacco use history (≤10 pack-years) who had their tumors genetically sequenced or mutational profiles analyzed.
Review Methods: Identified articles were screened by 2 reviewers. Quality of evidence was graded by the MINORS criteria for case-control studies; other studies were graded by assigning a level of evidence for gene mutation literature.
Results: Thirteen studies met our inclusion criteria, and 130 patients met our criteria for age and tobacco history. TP53 was the most commonly evaluated gene (10 of 13 studies) and the most frequently observed mutation. One study reported that nonsmokers had significantly fewer TP53 mutations, while 9 studies found no difference in the prevalence of TP53 mutations. No other mutations were found specific to this cohort.
Conclusions: TP53 mutations may occur at a similar rate in YLERs with OCSCC as compared with older patients or those with risk factors. However, few studies have aimed to characterize the genetic landscape of oral cavity tumors in this population, often with small sample sizes. Future studies are needed to explore unidentified genetic alterations leading to tumor susceptibility or alternative mechanisms of carcinogenesis.

PMID: 33210069 [PubMed]

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Development of auditory and language skills in children using cochlear implants with two signal processing strategies.

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Development of auditory and language skills in children using cochlear implants with two signal processing strategies.

Braz J Otorhinolaryngol. 2020 Nov - Dec;86(6):720-726

Authors: Melo TM, Yamaguti EH, Moret ALM, Costa OA, Lopes NBF

Abstract
INTRODUCTION: The increase in the spectral information offered by the sound processing strategy HiRes 120 has led to great expectations for the pediatric population. Due to a shorter duration of auditory deprivation and higher neural plasticity, children could benefit more substantially from the spectral information of this sound processing strategy.
OBJECTIVE: To compare auditory and language skills in Brazilian children with cochlear implants using the HiRes and HiRes 120 sound processing strategies.
METHODS: Thirty children, aged 1-3 years, with congenital hearing loss, were divided into two groups, according to the signal processing strategy adjusted at the time of the cochlear implant activation. The assessed children were matched according to chronological age and the time of the cochlear implant use. The auditory and language skills were evaluated longitudinally through the Infant-Toddler Meaningful Auditory Integration Scale and Production Infant Scale Evaluation, carried out before surgery, and 3, 6 and 12 months after device implantation. The Mann-Whitney test was applied for the comparison between the two groups with a 5% significance level.
RESULTS: The findings indicated development of hearing and language skills in the first year of cochlear implant use; however, there was no statistically significant difference in the evolution of such skills due to the adjusted processing strategy in the activation of the cochlear implant electrodes.
CONCLUSION: The development of auditory and language skills in the assessed children was similar during the entire study period, regardless of which signal processing strategy was used.

PMID: 31324459 [PubMed - indexed for MEDLINE]

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Genotype-phenotype correlation: Inheritance and variant-type infer pathogenicity in IQSEC2 gene.

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Genotype-phenotype correlation: Inheritance and variant-type infer pathogenicity in IQSEC2 gene.

Eur J Med Genet. 2020 Mar;63(3):103735

Authors: Barrie ES, Cottrell CE, Gastier-Foster J, Hickey SE, Patel AD, Santoro SL, Alfaro MP

Abstract
Pathogenic variants in the IQSEC2 gene including nonsense, frameshift, splice-alterations, deletions, and missense changes have been identified in individuals with X-linked mental retardation. Although highly variable, clinical features may include hypotonia, moderate to severe delayed psychomotor development, intellectual disability, speech deficits, refractory seizures, autistic features, and stereotypical movements. Females with de novo variants have been described with classical features. In contrast, the phenotype in carrier females identified through an affected male may range from asymptomatic to mild intellectual disability. We present male (N = 2) and female (N = 3) probands ascertained via diagnostic exome sequencing with distinct variant types in the IQSEC2 gene encompassing a spectrum of phenotypic severity with patient sex, variant type and inheritance hypothesized to drive disease penetrance and expressivity. All of these patients demonstrated epilepsy, global developmental delays, intellectual disability, and constipation. Our data support that de novo, truncating variants correlate with severe disease in both female and male patients harboring an IQSEC2 alteration. Missense variants in male and female patients may account for a milder disease overall, with more severe symptoms in males than females. We also present the first confirmed case of parental mosaicism, which has implications regarding counseling for recurrence risk. These data further delineate a genotype-phenotype correlation of IQSEC2 variation.

PMID: 31415821 [PubMed - indexed for MEDLINE]

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Electrically evoked ABR during cochlear implantation and postoperative development of speech and hearing abilities in infants with common cavity deformity as a type of inner ear malformation.

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Electrically evoked ABR during cochlear implantation and postoperative development of speech and hearing abilities in infants with common cavity deformity as a type of inner ear malformation.

Acta Otolaryngol. 2020 Jan;140(1):14-21

Authors: Kaga K, Minami S, Enomoto C

Abstract
Background: The electrically evoked auditory brainstem response (eABR) during cochlear implantation in common cavity (CC) deformity has not been clinically well studied.Aim/Objective: To investigate the eABR wave configuration during cochlear implantation, the postoperative development of hearing, and educational settings in infants with CC deformity.Materials and Methods: Nine infants who were congenitally deaf and found to have CC deformity and suspected cochlear nerve deficiency by temporal bone CT and MRI were studied. All of them underwent sequential and unilateral cochlear implantation and their eABRs were recorded during the surgery. The postoperative development was followed up.Results: eABRs of all the nine infants with CC deformity showed that the mean peak of the evoked wave V (eV) was the same as that in controls at latencies but was twofold higher than that in controls at thresholds and their postoperative hearing thresholds improved markedly.Conclusion and Signi ficance: The brainstem auditory pathways of the infants were considered intact on the basis of the eV peak latencies in the eABRs. The postoperative development of their speech and hearing abilities and their educational settings varied, probably because of the twofold higher thresholds of their eABRs and limited number of auditory neural units.

PMID: 31762359 [PubMed - indexed for MEDLINE]

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Multidisciplinary guidance for safe tracheostomy care during the COVID-19 pandemic: the NHS National Patient Safety Improvement Programme (NatPatSIP).

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Multidisciplinary guidance for safe tracheostomy care during the COVID-19 pandemic: the NHS National Patient Safety Improvement Programme (NatPatSIP).

Anaesthesia. 2020 12;75(12):1659-1670

Authors: McGrath BA, Ashby N, Birchall M, Dean P, Doherty C, Ferguson K, Gimblett J, Grocott M, Jacob T, Kerawala C, Macnaughton P, Magennis P, Moonesinghe R, Twose P, Wallace S, Higgs A

Abstract
The COVID-19 pandemic is causing a significant increase in the number of patients requiring relatively prolonged invasive mechanical ventilation and an associated surge in patients who need a tracheostomy to facilitate weaning from respiratory support. In parallel, there has been a global increase in guidance from professional bodies representing staff who care for patients with tracheostomies at different points in their acute hospital journey, rehabilitation and recovery. Of concern are the risks to healthcare staff of infection arising from tracheostomy insertion and caring for patients with a tracheostomy. Hospitals are also facing extraordinary demands on critical care services such that many patients who require a tracheostomy will be managed outside established intensive care or head and neck units and cared for by staff with little tracheostomy experience. These concerns led NHS England and NHS Improvement to expedite the National Patient Safety Improvement Programme' s 'Safe Tracheostomy Care' workstream as part of the NHS COVID-19 response. Supporting this workstream, UK stakeholder organisations involved in tracheostomy care were invited to develop consensus guidance based on: expert opinion; the best available published literature; and existing multidisciplinary guidelines. Topics with direct relevance for frontline staff were identified. This consensus guidance includes: infectivity of patients with respect to tracheostomy indications and timing; aerosol-generating procedures and risks to staff; insertion procedures; and management following tracheostomy.

PMID: 32396986 [PubMed - indexed for MEDLINE]

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Predicting treatment outcomes for bilinguals with aphasia using computational modeling: Study protocol for the PROCoM randomised controlled trial.

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Predicting treatment outcomes for bilinguals with aphasia using computational modeling: Study protocol for the PROCoM randomised controlled trial.

BMJ Open. 2020 Nov 18;10(11):e040495

Authors: Peñaloza C, Dekhtyar M, Scimeca M, Carpenter E, Mukadam N, Kiran S

Abstract
INTRODUCTION: Bilinguals with aphasia (BWA) present varying degrees of lexical access impairment and recovery across their two languages. Because both languages may benefit from therapy, identifying the optimal target language for treatment is a current challenge for research and clinical practice. Prior research has demonstrated that the BiLex computational model can accurately simulate lexical access in healthy bilinguals, and language impairment and treatment response in bilingual aphasia. Here, we aim to determine whether BiLex can predict treatment outcomes in BWA in the treated and the untreated language and compare these outcome predictions to determine the optimal language for rehabilitation.
METHODS AND ANALYSIS: The study involves a prospective parallel-group, double-blind, randomised controlled trial. Forty-eight Spanish-English BWA will receive 20 sessions of semantic treatment for lexical retrieval deficits in one of their languages and will complete assessments in both languages prior and after treatment. Participants will be randomly assigned to an experimental group receiving treatment in the optimal language determined by the model or a control group receiving treatment in the language opposite to the model's recommendation. Primary treatment outcomes include naming probes while secondary treatment outcomes include tests tapping additional language domains. Treatment outcomes will be compared across the two groups using 2×2 mixed effect models for repeated measures Analysis of variance (ANOVA) on metrics of treatment effects commonly employed in rehabilitation studies (ie, effect size and percentage change).
ETHICS AND DISSEMINATION: All procedures included in this protocol (protocol number 29, issue date: 19 March 2019) were approved by the Boston University Charles River Campus Institutional Review Board at Boston, Massachusetts (reference number: 4492E). The results of this study will be published in peer-reviewed scientific journals and will be presented at national and international conferences.
TRIAL REGISTRATION NUMBER: NCT02916524.

PMID: 33208330 [PubMed - in process]

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The effects of age on resting-state BOLD signal variability is explained by cardiovascular and cerebrovascular factors.

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The effects of age on resting-state BOLD signal variability is explained by cardiovascular and cerebrovascular factors.

Psychophysiology. 2020 Nov 18;:e13714

Authors: Tsvetanov KA, Henson RNA, Jones PS, Mutsaerts H, Fuhrmann D, Tyler LK, Cam-CAN, Rowe JB

Abstract
Accurate identification of brain function is necessary to understand neurocognitive aging, and thereby promote health and well-being. Many studies of neurocognitive aging have investigated brain function with the blood-oxygen level-dependent (BOLD) signal measured by functional magnetic resonance imaging. However, the BOLD signal is a composite of neural and vascular signals, which are differentially affected by aging. It is, therefore, essential to distinguish the age effects on vascular versus neural function. The BOLD signal variability at rest (known as resting state fluctuation amplitude, RSFA), is a safe, scalable, and robust means to calibrate vascular responsivity, as an alternative to breath-holding and hypercapnia. However, the use of RSFA for normalization of BOLD imaging assumes that age differences in RSFA reflecting only vascular factors, rather than age-related differences in neural function (activity) or neuronal loss (atrophy). Previous studies indicate that two vascular factors, cardiovascular health (CVH) and cerebrovascular function, are insufficient when used alone to fully explain age-related differences in RSFA. It remains possible that their joint consideration is required to fully capture age differences in RSFA. We tested the hypothesis that RSFA no longer varies with age after adjusting for a combination of cardiovascular and cerebrovascular measures. We also tested the hypothesis that RSFA variation with age is not associated with atrophy. We used data from the population-based, lifespan Cam-CAN cohort. After controlling for cardiovascular and cerebrovascular estimates alone, the residual variance in RSFA across individuals was significantly associated with age. However, when controlling for both cardiovascular and cerebrovascular estimates, the variance in RSFA was no longer associated with age. Grey matter volumes did not explain age differences in RSFA, after controlling for CVH. The results were consistent between voxel-l evel analysis and independent component analysis. Our findings indicate that cardiovascular and cerebrovascular signals are together sufficient predictors of age differences in RSFA. We suggest that RSFA can be used to separate vascular from neuronal factors, to characterize neurocognitive aging. We discuss the implications and make recommendations for the use of RSFA in the research of aging.

PMID: 33210312 [PubMed - as supplied by publisher]

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