Rapid Increase in Neural Conduction Time in the Adult Human Auditory Brainstem Following Sudden Unilateral Deafness

Individuals with sudden unilateral deafness offer a unique opportunity to study plasticity of the binaural auditory system in adult humans. Stimulation of the intact ear results in increased activity in the auditory cortex. However, there are no reports of changes at sub-cortical levels in humans. Therefore, the aim of the present study was to investigate changes in sub-cortical activity immediately before and after the onset of surgically induced unilateral deafness in adult humans. Click-evoked auditory brainstem responses (ABRs) to stimulation of the healthy ear were recorded from ten adults during the course of translabyrinthine surgery for the removal of a unilateral acoustic neuroma. This surgical technique always results in abrupt deafferentation of the affected ear. The results revealed a rapid (within minutes) reduction in latency of wave V (mean pre = 6.55 ms; mean post = 6.15 ms; p < 0.001). A latency reduction was also observed for wave III (mean pre = 4.40 ms; mean post = 4.13 ms; p < 0.001). These reductions in response latency are consistent with functional changes including disinhibition or/and more rapid intra-cellular signalling affecting binaurally sensitive neurons in the central auditory system. The results are highly relevant for improved understanding of putative physiological mechanisms underlying perceptual disorders such as tinnitus and hyperacusis.     

In vivo epigenetic effects induced by engineered nanomaterials: A case study of copper oxide and laser printer-emitted engineered nanoparticles

Evidence continues to grow on potential environmental health hazards associated with engineered nanomaterials (ENMs). While the geno- and cytotoxic effects of ENMs have been investigated, their potential to target the epigenome remains largely unknown. The aim of this study is two-fold: 1) determining whether or not industry relevant ENMs can affect the epigenome in vivo and 2) validating a recently developed in vitro epigenetic screening platform for inhaled ENMs. Laser printer-emitted engineered nanoparticles (PEPs) released from nano-enabled toners during consumer use and copper oxide (CuO) were chosen since these particles induced significant epigenetic changes in a recent in vitro companion study. In this study, the epigenetic alterations in lung tissue, alveolar macrophages and peripheral blood from intratracheally instilled mice were evaluated. The methylation of global DNA and transposable elements (TEs), the expression of the DNA methylation machinery and TEs, in addition to general toxicological effects in the lung were assessed. CuO exhibited higher cell-damaging potential to the lung, while PEPs showed a greater ability to target the epigenome. Alterations in the methylation status of global DNA and TEs, and expression of TEs and DNA machinery in mouse lung were observed after exposure to CuO and PEPs. Additionally, epigenetic changes were detected in the peripheral blood after PEPs exposure. Altogether, CuO and PEPs can induce epigenetic alterations in a mouse experimental model, which in turn confirms that the recently developed in vitro epigenetic platform using macrophage and epithelial cell lines can be successfully utilized in the epigenetic screening of ENMs.     

Congenital focal abnormalities of the retina and retinal pigment epithelium

This paper reviews the published literature on a group of developmental disorders of the retina and retinal pigment epithelium which result in focal abnormalities in one or both eyes. They are often asymptomatic, found on routine examination and are generally non-progressive. Some are associated with other systemic abnormalities.Subject terms: Retinal diseases, Eye abnormalities     

Group testing in mediation analysis

We consider the scenario where there is an exposure, multiple biologically defined sets of biomarkers, and an outcome. We propose a new two-step procedure that tests if any of the sets of biomarkers mediate the exposure/outcome relationship, while maintaining a prespecified familywise error rate. The first step of the proposed procedure is a screening step that removes all groups that are unlikely to be strongly associated with both the exposure and the outcome. The second step adapts recent advances in postselection inference to test if there are true mediators in each of the remaining candidate sets. We use simulation to show that this simple two-step procedure has higher statistical power to detect true mediating sets when compared with existing procedures. We then use our two-step procedure to identify a set of Lysine-related metabolites that potentially mediate the known relationship between increased body mass index and the increased risk of estrogen-receptor positive breast cancer in postmenopausal women.     

The Relationship between Self-Efficacy,Functional Exercise Capacity and Physical Activity in People with COPD: A Systematic Review and Meta-Analyses

Abstract

The purpose of this study was to investigate the strength of the relationships between self-efficacy and (i) functional exercise capacity and (ii) physical activity in chronic obstructive pulmonary disease (COPD), and whether self-efficacy assessment type (i.e., COPD symptoms, exercise-task, exercise-barrier, general, falls) and physical activity assessment type (i.e., self-report vs. objective) are moderators. A systematic search of COPD and self-efficacy concepts was conducted using eight databases from inception to 23 January 2019. Studies were included if they provided correlation coefficients of the relationship between self-efficacy and functional exercise capacity or physical activity, were conducted in adults diagnosed with COPD, and were published in English-language journals. A total of 14 correlation coefficients were included in the self-efficacy and functional exercise capacity meta-analysis, and 16 in the self-efficacy and physical activity meta-analysis. Data were screened, reviewed, and extracted independently by two reviewers, with discrepancies resolved by a third reviewer. Stronger self-efficacy was associated with better functional exercise capacity (weighted r?=?0.38, 95%CI [0.25, 0.50]), and greater physical activity (weighted r?=?0.25, 95%CI [0.17, 0.34]). Exercise-task self-efficacy had the strongest relationship to functional exercise capacity (weighted r?=?0.64, 95% CI [0.51, 0.73]). For physical activity, the type of self-efficacy most strongly related was inconclusive. In COPD, self-efficacy has a relationship to functional exercise capacity and physical activity, the strength of which is influenced by the choice of self-efficacy measure. An understanding of these relationships will assist clinicians in selecting the self-efficacy measure most closely related to the outcome of interest.