Genotype-Phenotype Correlations in TMPRSS3 (DFNB10/DFNB8) with Emphasis on Natural History.

BACKGROUND: Mutations in TMPRSS3 are an important cause of autosomal recessive non-syndromic hearing loss. The hearing loss associated with mutations in TMPRSS3 is characterized by phenotypic heterogeneity, ranging from mild to profound hearing loss, and is generally progressive. Clinical presentation and natural history of TMPRSS3 mutations vary significantly based on the location and type of mutation in the gene. Understanding these genotype-phenotype relationships and associated natural disease histories is necessary for the successful development and application of gene-based therapies and precision medicine approaches to DFNB8/10. The heterogeneous presentation of TMPRSS3-associated disease makes it difficult to identify patients clinically. As the body of literature on TMPRSS3-associated deafness grows, there is need for better categorization of the hearing phenotypes associated with specific mutations in the gene. SUMMARY: In this review, we summarize TMPRSS3 genotype-phenotype relationships including a thorough description of the natural history of patients with TMPRSS3-associated hearing loss to lay the groundwork for the future of TMPRSS3 treatment using molecular therapy. KEY MESSAGES: TMPRSS3 mutation is a significant cause of genetic hearing loss. All patients with TMPRSS3 mutation display severe-to-profound prelingual (DFNB10) or a postlingual (DFNB8) progressive sensorineural hearing loss. Importantly, TMPRSS3 mutations have not been associated with middle ear or vestibular deficits. The c.916G>A (p.Ala306Thr) missense mutation is the most frequently reported mutation across populations and should be further explored as a target for molecular therapy.

Usher Syndrome in the Inner Ear: Etiologies and Advances in Gene Therapy.

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.

Correction to: Patient-level factors are more salient than a legislation prohibiting minors in bars in predicting unintentional injury hospitalizations.

It was highlighted that in the original article [1] Fig. 1 and Fig. 2 were interchanged.

Patient-level factors are more salient than a legislation prohibiting minors in bars in predicting unintentional injury hospitalizations.

BACKGROUND: Alcohol related homicide, suicide and aggravated assault represent the largest costs for the state of Illinois. Previous research has examined the impact of some alcohol-related policies on youth alcohol use and alcohol-related harm in the United States but findings have been mixed. To our knowledge, no study has provided a detailed epidemiology of the relationship between the impacts of alcohol policies on unintentional injury in Illinois. Therefore, the purpose of this study is to determine whether a legislation that prohibit minors under 21 years old in establishments that serve alcohol is more salient than individual level factors in predicting hospitalization for traumatic unintentional injuries. METHODS: A retrospective observational study of data abstracted from 6,139 patients aged 10 to 19 hospitalized in Illinois Level I and Level II trauma centers. Patient data from 2006 to 2015 was linked with the city-level alcohol-related legislation (n = 514 cities). The response variable was whether a patient tested positive or negative for blood alcohol concentration (BAC) at the time of admission. Mixed-effects logistic regression analyses were conducted to model the patient and city level legislation effect of having a positive BAC test result on hospitalizations after adjusting for the legislation and patient factors. RESULTS: After adjustment, patients aged 15 to 19 and white patients who tested positive for BAC at the time of admission had the greater odds of hospitalization for traumatic alcohol-related unintentional injuries compared to patients who had a negative BAC test result. However, odds of hospitalization decreased for female patients and for those with private insurance, and over time, but a significant decrease in such hospitalizations occurred during 2010, 2014 and 2015. The alcohol-related legislation of interest was not a significant predictor of traumatic alcohol-related unintentional injury hospitalization. CONCLUSIONS: Patient-level covariates were significant predictors of traumatic alcohol-related unintentional injury hospitalization; an alcohol-related legislation may not reduce hospitalizations for young patients aged 10 to 19. Therefore, to prevent underage drinking and consequences, interventions should target sex/gender, race/ethnicity and focus on both individual and environmental strategies.

Adolescent and young adult couples' views of intravaginal practices: a qualitative analysis of a pilot study.

PURPOSE: In this study, we evaluated the risk behaviors that are drivers of the HIV epidemic among adolescent girls and young women in Zambia using a focus group research technique. SUBJECTS AND METHODS: Eighteen adolescent couples (n=18 females and 18 males) aged 16-24 participated in six focus groups discussions (3 per gender) convened at three health facilities in Lusaka, Zambia. Focus group moderators utilized a set of open-ended questions to guide the 60-minute sessions. The focus group audio recordings were transcribed, coded, and analyzed using qualitative content analysis in Nvivo 11. RESULTS: Three themes and four subthemes were identified relating to adolescent and young adult couples' knowledge, views, and male partner attitudes toward intravaginal practices (IVPs). The first theme, knowledge and rationale for IVPs, consisted of the subthemes relating to why adolescents and young adult couples engage in IVPs and assessed their knowledge of health risks associated with IVPs. The second theme, attitudes toward IVPs, consisted of the subtheme willingness to stop or support partner to discontinue IVP and practices toward IVP and strategies for changing. The third theme, strategies for changing IVPs, consisted of the subtheme raise awareness. CONCLUSION: IVPs used for cleaning purposes were perceived as essential to enhancing hygiene, health, and sexual satisfaction for both girls and boys. However, couples expressed concern about the health effects of IVPs used for tightening and a desire for learning more about this practice as well as stopping it.