Hearing Assessment of Orchestra and Marching Band Music Students

Musicians are a unique population in the world of audiology. It has been reported that on average, they exceed the recommended daily dose of noise exposure before the middle of their day. This significantly increases the risk of a permanent noise- or music- induced hearing loss. Such a hearing loss may influence their perception of timbre, pitch, and loudness thereby affecting their ability to play and enjoy music. Therefore, early identification of hearing problems is critical to this population. Twelve subjects with a variety of musical backgrounds and experiences were recruited for the study that had three primary purposes. The first was to design and implement a sensitive hearing assessment protocol to identify early signs of hearing loss in young musicians. The second was to determine the presence and significance of hearing loss, tinnitus (perception of sound when no actual external signal is present, commonly referred to as “ringing in the ears”), and hyperacusis (experience of everyday life sounds being perceived as intrusively loud, uncomfortable, or even painful) among musicians. The third was to determine if and when hearing protection devices were used in this population. All subjects completed a thorough case history that included history of noise exposure, musical background, habits and preferences for hearing protection device use, as well as screening for mental and physical health concerns. When indicated by patient responses to the case history, questionnaires about tinnitus, vertigo, hyperacusis, and hearing were administered and scored. The test battery included an evaluation of middle-ear function (otoscopy, tympanometry, and acoustic reflex), cochlear function based on distortion product otoacoustic emissions (DPOAEs), audiometry using conventional test frequencies (0.25-8 kHz) and extended high-frequencies (8-16 kHz), and the Words in Noise (WIN) test which uses monosyllabic words to quantify the loss of speech understanding in adverse listening situations. Results revealed that six subjects experience bothersome tinnitus (four, of whom had WIN scores in the mild range and three of whom reported hyperacusis). One of these seven also had absent DPOAES, absent acoustic reflexes, and a mild to moderate hearing loss from 6 – 16kHz. Case history indicated that the majority of subjects were not using hearing protection devices, suggesting a need for further education and preventative efforts. It also revealed a positive trend between anxiety/depression and tinnitus, hyperacusis, and dizziness severity. In our test protocol the WIN test was the most effective tool for identifying difficulty in adverse listening situations but asking subjects about experiencing tinnitus was a more reliable predictor of functional change to the auditory system (even in patients with thresholdsfrequencies). Together, these assessments could provide clinicians, musicians, and school administrators the value of music students using hearing protection when practicing, performing, or attending live shows

Serological humoral immunity following natural infection of children with high burden gastrointestinal viruses

Acute gastroenteritis (AGE) is a major cause of morbidity and mortality worldwide, resulting in an estimated 440,571 deaths of children under age 5 annually. Rotavirus, norovirus, and sapovirus are leading causes of childhood AGE. A successful rotavirus vaccine has reduced rotavirus hospitalizations by more than 50%. Using rotavirus as a guide, elucidating the determinants, breath, and duration of serological antibody immunity to AGE viruses, as well as host genetic factors that define susceptibility is essential for informing development of future vaccines and improving current vaccine candidates. Here, we summarize the current knowledge of disease burden and serological antibody immunity following natural infection to inform further vaccine development for these three high-burden viruses

Divergent pathogenetic outcomes in BALB/c mice following Omicron subvariant infection

Following the emergence of B.1.1.529 Omicron, the SARS-CoV-2 virus evolved into a significant number of sublineage variants that possessed numerous mutations throughout the genome, but particularly within the spike glycoprotein (S) gene. For example, the BQ.1.1 and the XBB.1 and XBB.1.5 subvariants contained 34 and 41 mutations in S, respectively. However, these variants elicited largely replication only or mild disease phenotypes in mice. To better model pathogenic outcomes and measure countermeasure performance, we developed mouse adapted versions (BQ.1.1 MA; XBB.1 MA; XBB.1.5 MA) that reflect more pathogenic acute phase pulmonary disease symptoms of SARS-CoV-2, as well as derivative strains expressing nano-luciferase (nLuc) in place of ORF7 (BQ.1.1 nLuc; XBB.1 nLuc; XBB.1.5 nLuc). Amongst the mouse adapted (MA) viruses, a wide range of disease outcomes were observed including mortality, weight loss, lung dysfunction, and tissue viral loads in the lung and nasal turbinates. Intriguingly, XBB.1 MA and XBB.1.5 MA strains, which contained identical mutations throughout except at position F486S/P in S, exhibited divergent disease outcomes in mice (Ao et al., 2023). XBB.1.5 MA infection was associated with significant weight loss and ∼45 % mortality across two independent studies, while XBB.1 MA infected animals suffered from mild weight loss and only 10 % mortality across the same two independent studies. Additionally, the development and use of nanoluciferase expressing strains provided moderate throughput for live virus neutralization assays. The availability of small animal models for the assessment of Omicron VOC disease potential will enable refined capacity to evaluate the efficacy of on market and pre-clinical therapeutics and interventions

Prefusion-stabilized SARS-CoV-2 S2-only antigen provides protection against SARS-CoV-2 challenge

Ever-evolving SARS-CoV-2 variants of concern (VOCs) have diminished the effectiveness of therapeutic antibodies and vaccines. Developing a coronavirus vaccine that offers a greater breadth of protection against current and future VOCs would eliminate the need to reformulate COVID-19 vaccines. Here, we rationally engineer the sequence-conserved S2 subunit of the SARS-CoV-2 spike protein and characterize the resulting S2-only antigens. Structural studies demonstrate that the introduction of interprotomer disulfide bonds can lock S2 in prefusion trimers, although the apex samples a continuum of conformations between open and closed states. Immunization with prefusion-stabilized S2 constructs elicits broadly neutralizing responses against several sarbecoviruses and protects female BALB/c mice from mouse-adapted SARS-CoV-2 lethal challenge and partially protects female BALB/c mice from mouse-adapted SARS-CoV lethal challenge. These engineering and immunogenicity results should inform the development of next-generation pan-coronavirus therapeutics and vaccines

Antigenic Site Immunodominance Redirection Following Repeat Variant Exposure

Human norovirus is a leading cause of acute gastroenteritis, driven by antigenic variants within the GII.4 genotype. Antibody responses to GII.4 vaccination in adults are shaped by immune memory. How children without extensive immune memory will respond to GII.4 vaccination has not been reported. Here, we characterized the GII.4 neutralizing antibody (nAb) landscape following natural infection using a surrogate assay and antigenic site chimera virus-like particles. We demonstrate that the nAb landscape changes with age and virus exposure. Among sites A, C, and G, nAbs from first infections are focused on sites A and C. As immunity develops with age/exposure, site A is supplemented with antibodies that bridge site A to sites C and G. Cross-site nAbs continue to develop into adulthood, accompanied by an increase in nAb to site G. Continued exposure to GII.4 2012 Sydney correlated with a shift to co-dominance of sites A and G. Furthermore, site G nAbs correlated with the broadening of nAb titer across antigenically divergent variants. These data describe fundamental steps in the development of immunity to GII.4 over a lifetime, and illustrate how the antigenicity of one pandemic variant could influence the pandemic potential of another variant through the redirection of immunodominant epitopes