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Objective: There is growing evidence that early application of a cochlear implant in children affected by profound congenital hearing loss is important for the development of an adequate auditory performance and language skills. The recent studies suggest that listening in noise shows a greater difficulty for listeners with CIs than for peers with normal hearing; especially in school where children are exposed to mean sound levels between 65 and 87 dB. Previous research has suggested that FM systems improved speech recognition performance in noise in children with CI/HA. The purpose of this study was to compare speech recognition performance in noise in children using CI or hearing aids with or without frequency modulation (FM) system or adaptive digital wireless radio transmission system. Materials and Methods: This study included 20 children with severe to profound hearing loss, ranging in age from 5.5 to 14 years, with unilateral CI (with or without contralateral hearing aid) or bilateral hearing aids. Word identification, phoneme identification and bisyllabic words and sentences recognition were tested at 70 dB speech in quiet and with competing noise at 70 dB noise levels. Participants (8 cochlear implant, 12 hearing aids) were tested with CI/HA alone and CI/HA coupled to FM receivers or wireless systems. Results : The results suggested that FM receivers provided significantly better speech-recognition performance in noise than the CI/HA alone, with a noise reduction of about 80%. The adaptive wireless systems provided better performance than FM systems at 70 dB competing noise of about 20%. Conclusion: The study supports the use of FM and wireless systems in classroom of students with hearing impairment. According data there is a benefit of the new digital adaptive wireless radio frequency transmission systems. [ABSTRACT FROM AUTHOR]

Amyotrophic lateral sclerosis (ALS) is an age-related neurodegenerative disease characterized by selective loss of motor neurons in the brainstem and spinal cord. Several genetic factors have been associated to ALS, ranging from causal genes and potential risk factors to disease modifiers. The search for pathogenic variants in these genes has mostly focused on single nucleotide variants (SNVs) while relatively understudied and not fully elucidated is the contribution of structural variants, such as copy number variations (CNVs). Here, we applied an exon-centric aCGH method to investigate, in sporadic ALS patients, the load of CNVs in 131 genes previously associated to ALS. Our approach revealed that CNV load, defined as the total number of CNVs or their size, was significantly higher in ALS cases than controls. About 87% of patients harbored multiple CNVs in ALS-related genes, and 75% structural variants compromised genes directly implicated in ALS pathogenesis (C9orf72, CHCHD10, EPHA4, FUS, HNRNPA1, KIF5A, NEK1, OPTN, PFN1, SOD1, TARDBP, TBK1, UBQLN2, UNC13A, VAPB, VCP). CNV load was also associated to higher onset age and disease progression rate. Although the contribution of individual CNVs in ALS is still unknown, their extensive load in disease-related genes may have relevant implications for the diagnostic, prognostic and therapeutical management of this devastating disorder., (© 2024. The Author(s).)

Background and Objectives : Although different hypotheses have been proposed over time, there is a dearth of information on factors able to predict the response to treatment for idiopathic sudden sensorineural hearing loss (ISSNHL) and hearing recovery. The aim of this study was to apply univariate and multivariate statistical models in a retrospective clinical setting of patients given therapy for ISSNHL at our tertiary academic audiological centers to investigate the prognostic value of clinical signs, symptoms, and comorbidities in relation to hearing recovery. Materials and Methods : The inclusion criteria were: history of ISSNHL diagnosed and treated at the Padova or Modena tertiary academic audiological centers; age ≥ 18 years; availability of clinical and audiological outcome data. The exclusion criteria were: hearing loss in acoustic schwannoma, endolymphatic hydrops, meningitis, trauma (head trauma, temporal bone fracture, acoustic trauma), barotrauma, perilymphatic fistula; exposure to noise levels ≥ 80 dB in the work environment; any unilateral or bilateral hearing loss (except for presbycusis) prior to ISSNHL diagnosis; any disorders affecting the external or middle ear; any previous ear surgery; refusal to make medical data available for research purposes. Eighty-six consecutive patients (38 females, 48 males; median age: 58 years; interquartile range: 47.00-69.00 years) were included. A systemic steroid therapy was administered to all patients, either orally with prednisone or intravenously with methylprednisolone. Second-line therapy included intratympanic steroid injections and/or hyperbaric oxygen therapy. Results : A multivariate logistic regression model was used, including the non-multicollinear clinical and audiological variables, which showed a p -value < 0.10 at the univariate analyses (namely age at diagnosis, time to diagnosis, oral steroid dose, and PTA on the affected side). Only PTA on the affected side retained its statistical significance (OR: 1.0615, 95% CI: 1.0185-1.1063, p = 0.005). Conclusions : The analysis of our data showed an association between the hearing threshold before treatment and the recovery from ISSNHL. Further studies on larger cohorts (especially in a prospective setting) are needed to shed more light on the prognostic role of clinical parameters in patients with ISSNHL. In a correct counseling setting, with regard to the patient's concern about not being able to recover hearing, it is important to offer perspectives of appropriate hearing rehabilitation approaches.

Amyotrophic lateral sclerosis (ALS) is a late-onset motor neuron disease with complex genetic basis and still no clear etiology. Multiple intertwined layers of immune system-related dysfunctions and neuroinflammatory mechanisms are emerging as substantial determinants in ALS onset and progression. In this review, we collect the increasingly arising evidence implicating four main CXC chemokines/cognate receptors signaling axes (CXCR1/2-CXCL1/2/8; CXCR3-CXCL9/10/11; CXCR4/7-CXCL12; CXCR5-CXCL13) in the pathophysiology of ALS. Findings in preclinical models implicate these signaling pathways in motor neuron toxicity and neuroprotection, while in ALS patients dysregulation of CXCLs/CXCRs has been shown at both central and peripheral levels. Immunological monitoring of CXC-ligands in ALS may allow tracking of disease progression, while pharmacological modulation of CXC-receptors provides a novel therapeutic strategy. A deeper understanding of the interplay between CXC-mediated neuroinflammation and ALS is crucial to advance research into treatments for this debilitating uncurable disorder., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Increasing evidence implicates decreased energy metabolism and mitochondrial dysfunctions among the earliest pathogenic events of Alzheimer's disease (AD). However, the molecular mechanisms underlying bioenergetic dysfunctions in AD remain, to date, largely unknown. In this work, we analyzed transcriptomic changes occurring in the hippocampus and retina of a Tg2576 AD mouse model and wild-type controls, evaluating their functional implications by gene set enrichment analysis. The results revealed that oxidative phosphorylation and mitochondrial-related pathways are significantly down-regulated in both tissues of Tg2576 mice, supporting the role of these processes in the pathogenesis of AD. In addition, we also analyzed transcriptomic changes occurring in Tg2576 mice treated with the 12A12 monoclonal antibody that neutralizes an AD-relevant tau-derived neurotoxic peptide in vivo . Our analysis showed that the mitochondrial alterations observed in AD mice were significantly reverted by treatment with 12A12mAb, supporting bioenergetic pathways as key mediators of its in vivo neuroprotective and anti-amyloidogenic effects. This study provides, for the first time, a comprehensive characterization of molecular events underlying the disrupted mitochondrial bioenergetics in AD pathology, laying the foundation for the future development of diagnostic and therapeutic tools.

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive and ultimately fatal neurodegenerative disease, characterized by a progressive depletion of upper and lower motor neurons (MNs) in the brain and spinal cord. The aberrant regulation of several PKC-mediated signal transduction pathways in ALS has been characterized so far, describing either impaired expression or altered activity of single PKC isozymes (α, β, ζ and δ). Here, we detailed the distribution and cellular localization of the ε-isozyme of protein kinase C (PKCε) in human postmortem motor cortex specimens and reported a significant decrease in both PKCε mRNA ( PRKCE ) and protein immunoreactivity in a subset of sporadic ALS patients. We furthermore investigated the steady-state levels of both pan and phosphorylated PKCε in doxycycline-activated NSC-34 cell lines carrying the human wild-type (WT) or mutant G93A SOD1 and the biological long-term effect of its transient agonism by Bryostatin-1. The G93A-SOD1 cells showed a significant reduction of the phosphoPKCε/panPKCε ratio compared to the WT. Moreover, a brief pulse activation of PKCε by Bryostatin-1 produced long-term survival in activated G93A-SOD1 degenerating cells in two different cell death paradigms (serum starvation and chemokines-induced toxicity). Altogether, the data support the implication of PKCε in ALS pathophysiology and suggests its pharmacological modulation as a potential neuroprotective strategy, at least in a subgroup of sporadic ALS patients.