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.

Molecular mechanisms governing the development of the mammalian cochlea, the hearing organ, remain largely unknown. Through genome sequencing in 3 subjects from 2 families with nonsyndromic cochlear aplasia, we identified homozygous 221-kb and 338-kb deletions in a noncoding region on chromosome 8 with an approximately 200-kb overlapping section. Genomic location of the overlapping deleted region started from approximately 350 kb downstream of GDF6, which codes for growth and differentiation factor 6. Otic lineage cells differentiated from induced pluripotent stem cells derived from an affected individual showed reduced expression of GDF6 compared with control cells. Knockout of Gdf6 in a mouse model resulted in cochlear aplasia, closely resembling the human phenotype. We conclude that GDF6 plays a necessary role in early cochlear development controlled by cis-regulatory elements located within an approximately 500-kb region of the genome in humans and that its disruption leads to deafness due to cochlear aplasia.

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.

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.

Hypertension (HTN) is a chronic condition that requires careful monitoring and management. Blood pressure readings in the clinic and self-reported blood pressure readings are often too intermittent to allow for careful management. Remote patient monitoring is a solution that may have positive impacts on HTN management. Individuals at cardiac and primary care clinics were prescribed a remote patient-monitoring (RPM) program. Patients were sent blood pressure monitors that were enabled to transmit data over cellular networks. We reviewed trends in HTN management retrospectively in patients who had previously been on conventional therapy for a year and participated in RPM for a minimum of 90 days. There were 6595 patients enrolled, and the mean duration on RPM was 289 days. A total of 4370 participants (66.3%) had uncontrolled HTN, and 2476 (37.5%) had stage 2 HTN. After at least 90 days on the RPM program, the number of patients with uncontrolled HTN reduced to 2648 (40.2%, p < 0.01), and the number of patients with stage 2 HTN reduced to 1261 (19.1%, p < 0.01). Systolic blood pressure improved by 7.3 mmHg for all patients and 16.7 mmHg for stage 2 HTN. There was improvement in mean arterial pressure (MAP) in all patients with uncontrolled HTN by 8.5 mmHg (p < 0.0001). RPM is associated with improved HTN control and provides further evidence supporting telehealth programs which can aid in chronic disease management.

The evolution of psychotherapeutic treatments from Freud to digitally administered evidence-based treatments reflects a history of progressive advance. This history is characterized by identification of problems with the current state of the art, followed by solutions inspired and supported by advances in basic science and technology leading to subsequent recognition of other limitations revealed by the new advance. The common thread running through this process is (a) increasing specificity of the psychotherapeutic interventions, (b) increasing evidence of efficacy and safety, (c) increasing integrity and reliability in the delivery of the intervention, (d) increased equality of access, and (e) recognition of the need for regulation to provide protection for the public from unsafe or ineffective products. This evolution of psychotherapeutic treatments, not surprisingly, has been foreshadowed by the precursor history of the evolution of pharmacologic treatment. Although intellectual history is lumpy and does not sort itself into discrete and coherent epochs, such sorting is a useful heuristic for describing the advance of medicine and the therapeutic enterprise. This paper will discuss six successive epochs of psychotherapy. For each it will discuss the problem of the preceding era it sought to solve, the advance it brought to the field, the emerging science and technology that supported that advance, and the precursor development in pharmacological treatments that foreshadowed that epoch of psychotherapy. Finally, it will conclude with some observations about the proximate future.