No abstract

Progressive non-syndromic sensorineural hearing loss (PNSHL) is the most common cause of sensory impairment, affecting more than a third of individuals over the age of 65. PNSHL includes noise-induced hearing loss (NIHL) and inherited forms of deafness, among which is delayed-onset autosomal dominant hearing loss (AD PNSHL). PNSHL is a prime candidate for genetic therapies due to the fact that PNSHL has been studied extensively, and there is a potentially wide window between identification of the disorder and the onset of hearing loss. Several gene therapy strategies exist that show potential for targeting PNSHL, including viral and non-viral approaches, and gene editing versus gene-modulating approaches. To fully explore the potential of these therapy strategies, a faithful in vitro model of the human inner ear is needed. Such models may come from induced pluripotent stem cells (iPSCs). The development of new treatment modalities by combining iPSC modeling with novel and innovative gene therapy approaches will pave the way for future applications leading to improved quality of life for many affected individuals and their families.

Given the interdependence of multiple factors in age-related vestibular loss (e.g., balance, vision, cognition), it is important to examine the individual contributions of these factors with ARVL. While the relationship between the vestibular and visual systems has been well studied ( Bronstein et al., 2015 ), little is known about the association of the peripheral vestibular system with neurodegenerative disorders ( Cronin et al., 2017 ). Further, emerging research developments implicate the vestibular system as an opportunity for examining brain function beyond balance, and into other areas, such as cognition and psychological functioning. Additionally, the bidirectional impact of psychological functioning is understudied in ARVL. Recognition of ARVL as part of a multifaceted aging process will help guide the development of integrated interventions for patients who remain at risk for decline. In this review, we will discuss a wide variety of characteristics of the peripheral vestibular system and ARVL, how it relates to neurodegenerative diseases, and correlations between ARVL and balance, vision, cognitive, and psychological dysfunction. We also discuss clinical implications as well as future directions for research, with an emphasis on improving care for patients with ARVL.

Vaginal dysbiosis-induced by an overgrowth of anaerobic bacteria is referred to as bacterial vaginosis (BV). The dysbiosis is associated with an increased risk for acquisition of sexually transmitted infections. Women with symptomatic BV are treated with oral metronidazole (MET), but its effectiveness remains to be elucidated. This study used whole-genome sequencing (WGS) to determine the changes in the microbiota among women treated with MET. WGS was conducted on DNA obtained from 20 vaginal swabs collected at four time points over 12 months from five randomly selected African American (AA) women. The baseline visit included all women who were diagnosed with asymptomatic BV and were untreated. All subjects were tested subsequently once every 2 months and received a course of MET for each BV episode during the 12 months. The BV status was classified according to Nugent scores (NSs) of vaginal smears. The microbial and resistome profiles were analysed along with the sociodemographic metadata. Despite treatment, none of the five participants reverted to normal vaginal flora — two were consistently positive for BV, and the rest experienced episodic cases of BV. WGS analyses showed Gardnerella spp. as the most abundant organism. After treatment with MET, there was an observed decline of Lactobacillus and Prevotella species. One participant had a healthy vaginal microbiota based on NS at one follow-up time point. Resistance genes including tetM and lscA were detected. Though limited in subjects, this study shows specific microbiota changes with treatment, presence of many resistant genes in their microbiota, and recurrence and persistence of BV despite MET treatment. Thus, MET may not be an effective treatment option for asymptomatic BV, and whole metagenome sequence would better inform the choice of antibiotics.

Hearing loss is the most common sensory disorder with ~466 million people worldwide affected, representing about 5% of the population. A substantial portion of hearing loss is genetic. Hearing loss can either be non-syndromic, if hearing loss is the only clinical manifestation, or syndromic, if the hearing loss is accompanied by a collage of other clinical manifestations. Usher syndrome is a syndromic form of genetic hearing loss that is accompanied by impaired vision associated with retinitis pigmentosa and, in many cases, vestibular dysfunction. It is the most common cause of deaf-blindness. Currently cochlear implantation or hearing aids are the only treatments for Usher-related hearing loss. However, gene therapy has shown promise in treating Usher-related retinitis pigmentosa. Here we review how the etiologies of Usher-related hearing loss make it a good candidate for gene therapy and discuss how various forms of gene therapy could be applied to Usher-related hearing loss.