Risk factors for hearing loss in children: A systematic literature review and meta-analysis protocol

Background: Hearing loss in newborns and children is a public health concern, due to high prevalence and negative effects on their development. Early detection and intervention of childhood hearing loss may mitigate these negative effects. Population-based newborn hearing screening programs have been established worldwide to identify children at risk for congenital hearing loss and to follow children at risk for late onset or progressive hearing loss. This article presents the protocol for a systematic review that aims to review the risk factors associated with permanent hearing loss in children, including congenital, early, or late onset. Risk factors associated with progressive hearing loss will be investigated as a secondary aim. Methods: Scientific literature from the following databases will be investigated: MEDLINE, Ovid MEDLINE(R) Daily and Ovid MEDLINE(R), Embase, and CINAHL. The primary outcome is a permanent bilateral or unilateral hearing loss with congenital onset or onset during childhood (birth to 18 years). The secondary outcome is progressive hearing loss. Studies must report data on risk factors associated with permanent hearing loss; risk factors may be present at birth or later and result in immediate or delayed hearing loss. Randomized controlled trials, quasi-experimental studies, nonrandomized comparative and non-comparative studies, and case series will be included. The risk of bias will be assessed using the Qualitative Assessment Tool for Quantitative Studies (McMaster University). If aggregation of data is possible for a subsection of studies, we will pool data using meta-analysis techniques. If aggregation of data is not possible, a qualitative synthesis will be presented. We will assess the quality and strength of the overall body of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE). The systematic review follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations. Discussion: The resulting information will inform the update of a provincial audiological surveillance protocol for the Ontario Infant Hearing Program and will be applicable to early hearing detection and intervention (EHDI) programs worldwide. Systematic review registration: We have registered the protocol in the International Prospective Register of Systematic Reviews (PROSPERO), registration number CRD42018104121

“It gives me confidence”: Caregiver Coaching From the Perspective of Families of Children Who Are Deaf or Hard of Hearing

Caregiver coaching is utilized in early intervention services with families of children who are deaf or hard of hearing to increase caregivers’ skills and confidence in supporting their child’s language development, but few studies have examined coaching from the perspective of the caregivers. The purpose of this study was to increase understanding of caregivers’ experiences of coaching in the context of listening and spoken language intervention services. Using semi-structured, qualitative interviews, this study examined 13 caregivers’ perspectives at three intervention sites in the US and Canada. Results indicate that caregivers perceive that practitioner characteristics, expectations, and the evolution of the coaching relationship over time contribute to a positive caregiver coaching relationship. This study contributes to the understanding of the caregiver coaching experience and has implications for new and experienced practitioners working to improve their practice by establishing and strengthening collaborative caregiver coaching relationships with the families they serve

“It’s About Walking Alongside a Family”: Practitioner Perspectives on Caregiver Coaching With Families of Children Who Are Deaf or Hard of Hearing

Practitioners utilize caregiver coaching in early intervention services, but coaching principles and practices are not well understood in the context of listening and spoken language (LSL) services with families of children who are deaf or hard of hearing. The purpose of this study was to examine practitioners’ experiences with coaching, including definitions, training, and practices they utilize in their work with families. Using semi-structured, qualitative interviews and video observation discussions, this study examined the perspectives of 14 practitioners providing LSL services to families at three intervention sites in the US and Canada. Results indicate that practitioners’ underlying beliefs about their coaching proficiency and caregivers’ capacity impact their coaching practices and how they engage with caregivers. Results highlight practices such as mentoring and accountability that supported practitioners’ coaching skills. This study contributes to the understanding of caregiver coaching in LSL practice and has implications for practitioners working to improve their coaching skills, which may improve LSL services and optimize child outcomes

Apoptosis signal-regulating kinase-1 promotes inflammasome priming in macrophages

© 2019 the American Physiological Society. previously showed that mice deficient in apo-ptosis signal-regulating kinase-1 (ASK1) were partially protected against ventilator-induced lung injury. Because ASK1 can promote both cell death and inflammation, we hypothesized that ASK1 activation regulates inflammasome-mediated inflammation. Mice deficient in ASK1 expression (ASK1 +/+ ) exhibited significantly less inflammation and lung injury (as measured by neutrophil infiltration, IL-6, and IL-1β) in response to treatment with inhaled lipopolysaccharide (LPS) compared with wild-type (WT) mice. To determine whether this proinflammatory response was mediated by ASK1, we investigated inflammasome-mediated responses to LPS in primary macrophages and bone marrow-derived macrophages (BMDMs) from WT and ASK1 +/+ mice, as well as the mouse alveolar macrophage cell line MH-S. Cells were treated with LPS alone for priming or LPS followed by ATP for activation. When macrophages were stimulated with LPS followed by ATP to activate the inflammasome, we found a significant increase in secreted IL-1β from WT cells compared with ASK1-deficient cells. LPS priming stimulated an increase in NOD-like receptor 3 (NLRP3) and pro-IL-1β in WT BMDMs, but expression of NLRP3 was significantly decreased in ASK1 +/+ BMDMs. Subsequent ATP treatment stimulated an increase in cleaved caspase-1 and IL-1β in WT BMDMs compared with ASK1 +/+ BMDMs. Similarly, treatment of MH-S cells with LPS + ATP caused an increase in both cleaved caspase-1 and IL-1β that was diminished by the ASK-1 inhibitor NQDI1. These results demonstrate, for the first time, that ASK1 promotes inflammasome priming

Structural mechanism for gating of a eukaryotic mechanosensitive channel of small conductance

Mechanosensitive ion channels transduce physical force into electrochemical signaling that underlies an array of fundamental physiological processes, including hearing, touch, proprioception, osmoregulation, and morphogenesis. The mechanosensitive channels of small conductance (MscS) constitute a remarkably diverse superfamily of channels critical for management of osmotic pressure. Here, we present cryo-electron microscopy structures of a MscS homolog from Arabidopsis thaliana, MSL1, presumably in both the closed and open states. The heptameric MSL1 channel contains an unusual bowl-shaped transmembrane region, which is reminiscent of the evolutionarily and architecturally unrelated mechanosensitive Piezo channels. Upon channel opening, the curved transmembrane domain of MSL1 flattens and expands. Our structures, in combination with functional analyses, delineate a structural mechanism by which mechanosensitive channels open under increased membrane tension. Further, the shared structural feature between unrelated channels suggests the possibility of a unified mechanical gating mechanism stemming from membrane deformation induced by a non-planar transmembrane domain

RESEARCH Open Access

Involving consumers and the community in the development of a diagnostic instrument for fetal alcohol spectrum disorders in Australi

UV Absorption Lines from High-Velocity Gas in the Vela Supernova Remnant: New insights from STIS Echelle Observations of HD72089

The star HD72089 is located behind the Vela supernova remnant and shows a complex array of high and low velocity interstellar absorption features arising from shocked clouds. A spectrum of this star was recorded over the wavelength range 1196.4 to 1397.2 Angstroms at a resolving power lambda/Delta lambda = 110,000 and signal-to-noise ratio of 32 by STIS on the Hubble Space Telescope. We have identified 7 narrow components of C I and have measured their relative populations in excited fine-structure levels. Broader features at heliocentric velocities ranging from -70 to +130 km/s are seen in C II, N I, O I, Si II, S II and Ni II. In the high-velocity components, the unusually low abundances of N I and O I, relative to S II and Si II, suggest that these elements may be preferentially ionized to higher stages by radiation from hot gas immediately behind the shock fronts.Comment: 11 pages, 2 figures, Latex. Submitted for the special HST ERO issue of the Astrophysical Journal Letter

Deficiency of the two-pore-domain potassium channel TREK-1 promotes hyperoxia-induced lung injury

Copyright © 2014 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins. Objectives: We previously reported the expression of the twoporedomain K+ channel TREK-1 in lung epithelial cells and proposed a role for this channel in the regulation of alveolar epithelial cytokine secretion. In this study, we focused on investigating the role of TREK-1 in vivo in the development of hyperoxia-induced lung injury. Design: Laboratory animal experiments. Setting: University research laboratory. Subjects: Wild-type and TREK-1-deficient mice. Interventions: Mice were anesthetized and exposed to 1) room air, no mechanical ventilation, 2) 95% hyperoxia for 24 hours, and 3) 95% hyperoxia for 24 hours followed by mechanical ventilation for 4 hours. Measurements and Main Results: Hyperoxia exposure accentuated lung injury in TREK-1-deficient mice but not controls, resulting in increase in lung injury scores, bronchoalveolar lavage fluid cell numbers, and cellular apoptosis and a decrease in quasi-static lung compliance. Exposure to a combination of hyperoxia and injurious mechanical ventilation resulted in further morphological lung damage and increased lung injury scores and bronchoalveolar lavage fluid cell numbers in control but not TREK-1-deficient mice. At baseline and after hyperoxia exposure, bronchoalveolar lavage cytokine levels were unchanged in TREK-1-deficient mice compared with controls. Exposure to hyperoxia and mechanical ventilation resulted in an increase in bronchoalveolar lavage interleukin-6, monocyte chemotactic protein-1, and tumor necrosis factor-á levels in both mouse types, but the increase in interleukin-6 and monocyte chemotactic protein-1 levels was less prominent in TREK-1-deficient mice than in controls. Lung tissue macrophage inflammatory protein-2, keratinocytederived cytokine, and interleukin-1β gene expression was not altered by hyperoxia in TREK-1-deficient mice compared with controls. Furthermore, we show for the first time TREK-1 expression on alveolar macrophages and unimpaired tumor necrosis factor-á secretion from TREK-1-deficient macrophages. Conclusions: TREK-1 deficiency resulted in increased sensitivity of lungs to hyperoxia, but this effect is less prominent if overwhelming injury is induced by the combination of hyperoxia and injurious mechanical ventilation. TREK-1 may constitute a new potential target for the development of novel treatment strategies against hyperoxiainduced lung injury

Genetic characterization of outbred Sprague Dawley rats and utility for genome-wide association studies

Sprague Dawley (SD) rats are among the most widely used outbred laboratory rat populations. Despite this, the genetic characteristics of SD rats have not been clearly described, and SD rats are rarely used for experiments aimed at exploring genotype-phenotype relationships. In order to use SD rats to perform a genome-wide association study (GWAS), we collected behavioral data from 4,625 SD rats that were predominantly obtained from two commercial vendors, Charles River Laboratories and Harlan Sprague Dawley Inc. Using double-digest genotyping-by-sequencing (ddGBS), we obtained dense, high-quality genotypes at 291,438 SNPs across 4,061 rats. This genetic data allowed us to characterize the variation present in Charles River vs. Harlan SD rats. We found that the two populations are highly diverged (FST > 0.4). Furthermore, even for rats obtained from the same vendor, there was strong population structure across breeding facilities and even between rooms at the same facility. We performed multiple separate GWAS by fitting a linear mixed model that accounted for population structure and using meta-analysis to jointly analyze all cohorts. Our study examined Pavlovian conditioned approach (PavCA) behavior, which assesses the propensity for rats to attribute incentive salience to reward-associated cues. We identified 46 significant associations for the various metrics used to define PavCA. The surprising degree of population structure among SD rats from different sources has important implications for their use in both genetic and non-genetic studies