The Effect of Hearing Aids and Cochlear Implants on Children’s Development of Phonological Awareness Skills: A Review of the Evidence

Poster presentation at the Georgia Undergraduate Research Conference, University of North Georgia, Gainesville, GA. Purpose:The purpose of this review is to determine if phonological awareness skill development varies based on intervention with cochlear implants (CIs) versus hearing aids in young children by the time they enter kindergarten. Phonological awareness is the ability to manipulate and analyze speech sounds (Werfel, Douglas, & Ackal, 2016) and contributes to literacy development. Evaluating phonological awareness skills determines whether children using hearing aids or CIs have difficulty identifying sounds in words (Ching & Cupples, 2015). Hearing aid and CI users rely on the auditory input from their devices to understand speech sounds. These devices can improve spoken and written communication for individuals with profound sensorineural hearing loss. However, even with these devices, children with hearing impairment are at risk for phonological awareness deficits. A critical difference between them is their invasiveness. Hearing aids amplify the sounds the child has difficulty hearing (Waltzman, 2006) through a mechanism worn behind or in the ear, whereas CIs convert sound waves to electrical impulses in a way that mimics natural hearing. Because profound sensorineural hearing loss damages the hair cells in the inner ear, specifically the cochlea, CIs are surgically implanted to directly stimulate the auditory nerve, bypassing the damaged inner ear (Martin & Clark, 2006). Method:A systematic review of the best available literature is currently underway. Potentially relevant literature has been identified by searching the following terms in Galileo: “hearing aids”, “cochlear implants”, “profound sensorineural hearing loss”, and “phonological awareness”. Initially, there were approximately 17,000 results. Search configuration tools were used to limit the results to full-text articles and scholarly/peer-reviewed articles within the years 2005 to 2016. This narrowed the results to 2,611 articles. These results will be further screened to identify the most relevant studies. Results/Conclusions:Currently, this review is in progress. Results/conclusions can potentially help parents make educated decisions on whether hearing aids or cochlear implants are the best option for the child’s phonological awareness development

GnRH-Regulated Expression of Jun and JUN Target Genes in Gonadotropes Requires a Functional Interaction between TCF/LEF Family Members and β-Catenin

GnRH regulates gonadotrope function through a complex transcriptional network that includes three members of the immediate early gene family: Egr1, Jun, and Atf3. These DNA-binding proteins act alone or in pairs to confer hormonal responsiveness to Cga, Lhb, Fshb, and Gnrhr. Herein we suggest that the transcriptional response of Jun requires a functional interaction between the T-cell factor (TCF)/lymphoid enhancer factor (LEF) family of DNA-binding proteins and β-catenin (officially CTNNB1), a coactivator of TCF/LEF. Supporting data include demonstration that GnRH increases activity of TOPflash, a TCF/LEF-dependent luciferase reporter, in LβT2 cells, a gonadotrope-derived cell line. Additional cotransfection experiments indicate that a dominant-negative form of TCF7L2 (TCFDN) that binds DNA, but not β-catenin, blocks GnRH induction of TOPflash. Overexpression of AXIN, an inhibitor of β-catenin, also reduces GnRH stimulation of TOPflash. Transduction of LβT2 cells with TCFDN adenoviruses diminishes GnRH stimulation of Jun mRNA without altering expression of Egr1 and Atf3, two other immediate early genes that confer GnRH responsiveness. Reduction of β-catenin in LβT2 cells, through stable expression of short hairpin RNA, also selectively compromises GnRH regulation of Jun expression and levels of JUN protein. Finally, overexpression of TCFDN attenuates GnRH regulation of Cga promoter activity, a known downstream target of JUN. Together, these results indicate that GnRH regulation of Jun transcription requires a functional interaction between TCF/LEF and β-catenin and that alteration of either impacts expression of JUN downstream targets such as Cga

NOD1 and NOD2 signalling links ER stress with inflammation

Endoplasmic reticulum (ER) stress is a major contributor to inflammatory diseases, such as Crohn disease and type 2 diabetes. ER stress induces the unfolded protein response, which involves activation of three transmembrane receptors, ATF6, PERK and IRE1α. Once activated, IRE1α recruits TRAF2 to the ER membrane to initiate inflammatory responses via the NF-κB pathway. Inflammation is commonly triggered when pattern recognition receptors (PRRs), such as Toll-like receptors or nucleotide-binding oligomerization domain (NOD)-like receptors, detect tissue damage or microbial infection. However, it is not clear which PRRs have a major role in inducing inflammation during ER stress. Here we show that NOD1 and NOD2, two members of the NOD-like receptor family of PRRs, are important mediators of ER-stress-induced inflammation in mouse and human cells. The ER stress inducers thapsigargin and dithiothreitol trigger production of the pro-inflammatory cytokine IL-6 in a NOD1/2-dependent fashion. Inflammation and IL-6 production triggered by infection with Brucella abortus, which induces ER stress by injecting the type IV secretion system effector protein VceC into host cells, is TRAF2, NOD1/2 and RIP2-dependent and can be reduced by treatment with the ER stress inhibitor tauroursodeoxycholate or an IRE1α kinase inhibitor. The association of NOD1 and NOD2 with pro-inflammatory responses induced by the IRE1α/TRAF2 signalling pathway provides a novel link between innate immunity and ER-stress-induced inflammation

National Landscape of Human Immunodeficiency Virus-Positive Deceased Organ Donors in the United States.

BackgroundOrgan transplantation from donors with human immunodeficiency virus (HIV) to recipients with HIV (HIV D+/R+) presents risks of donor-derived infections. Understanding clinical, immunologic, and virologic characteristics of HIV-positive donors is critical for safety.MethodsWe performed a prospective study of donors with HIV-positive and HIV false-positive (FP) test results within the HIV Organ Policy Equity (HOPE) Act in Action studies of HIV D+/R+ transplantation (ClinicalTrials.gov NCT02602262, NCT03500315, and NCT03734393). We compared clinical characteristics in HIV-positive versus FP donors. We measured CD4 T cells, HIV viral load (VL), drug resistance mutations (DRMs), coreceptor tropism, and serum antiretroviral therapy (ART) detection, using mass spectrometry in HIV-positive donors.ResultsBetween March 2016 and March 2020, 92 donors (58 HIV positive, 34 FP), representing 98.9% of all US HOPE donors during this period, donated 177 organs (131 kidneys and 46 livers). Each year the number of donors increased. The prevalence of hepatitis B (16% vs 0%), syphilis (16% vs 0%), and cytomegalovirus (CMV; 91% vs 58%) was higher in HIV-positive versus FP donors; the prevalences of hepatitis C viremia were similar (2% vs 6%). Most HIV-positive donors (71%) had a known HIV diagnosis, of whom 90% were prescribed ART and 68% had a VL <400 copies/mL. The median CD4 T-cell count (interquartile range) was 194/µL (77-331/µL), and the median CD4 T-cell percentage was 27.0% (16.8%-36.1%). Major HIV DRMs were detected in 42%, including nonnucleoside reverse-transcriptase inhibitors (33%), integrase strand transfer inhibitors (4%), and multiclass (13%). Serum ART was detected in 46% and matched ART by history.ConclusionThe use of HIV-positive donor organs is increasing. HIV DRMs are common, yet resistance that would compromise integrase strand transfer inhibitor-based regimens is rare, which is reassuring regarding safety