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BackgroundMultiple gaming apps exist under the dementia umbrella for skills such as navigation; however, an app to specifically investigate the role of hearing loss in the process of cognitive decline is yet to be designed. There is a demonstrable gap in the utilization of games to further the knowledge of the potential relationship between hearing loss and dementia. ObjectiveThis study aims to identify the needs, facilitators, and barriers in designing a novel auditory-cognitive training gaming app. MethodsA participatory design approach was used to engage key stakeholders across audiology and cognitive disorder specialties. Two rounds, including paired semistructured interviews and focus groups, were completed and thematically analyzed. ResultsA total of 18 stakeholders participated, and 6 themes were identified to inform the next stage of app development. These included congruence with hobbies, life getting in the way, motivational challenge, accessibility, addictive competition, and realism. ConclusionsThe findings can now be implemented in the development of the app. The app will be evaluated against outcome measures of speech listening in noise, cognitive and attentional tasks, quality of life, and usability.

SOX9 is a key transcription factor for testis determination and development. Mutations in and around the SOX9 gene contribute to Differences/Disorders of Sex Development (DSD). However, a substantial proportion of DSD patients lack a definitive genetic diagnosis. SOX9 target genes are potentially DSD-causative genes, yet only a limited subset of these genes has been investigated during testis development. We hypothesize that SOX9 target genes play an integral role in testis development and could potentially be causative genes in DSD. In this study, we describe a novel testicular target gene of SOX9, Trpc3. Trpc3 exhibits high expression levels in the SOX9-expressing male Sertoli cells compared to female granulosa cells in mouse fetal gonads between embryonic day 11.5 (E11.5) and E13.5. In XY Sox9 knockout gonads, Trpc3 expression is markedly downregulated. Moreover, culture of E11.5 XY mouse gonads with TRPC3 inhibitor Pyr3 resulted in decreased germ cell numbers caused by reduced germ cell proliferation. Trpc3 is also expressed in endothelial cells and Pyr3-treated E11.5 XY mouse gonads showed a loss of the coelomic blood vessel due to increased apoptosis of endothelial cells. In the human testicular cell line NT2/D1, TRPC3 promotes cell proliferation and controls cell morphology, as observed by xCELLigence and HoloMonitor real-time analysis. In summary, our study suggests that SOX9 positively regulates Trpc3 in mouse testes and TRPC3 may mediate SOX9 function during Sertoli, germ and endothelial cell development. [ABSTRACT FROM AUTHOR]

Chemotherapy induced ovarian failure and infertility is an important concern in female cancer patients of reproductive age or younger, and non-invasive, pharmacological approaches to maintain ovarian function are urgently needed. Given the role of reduced nicotinamide adenine dinucleotide phosphate (NADPH) as an essential cofactor for drug detoxification, we sought to test whether boosting the NAD(P)+ metabolome could protect ovarian function. We show that pharmacological or transgenic strategies to replenish the NAD+ metabolome ameliorates chemotherapy induced female infertility in mice, as measured by oocyte yield, follicle health, and functional breeding trials. Importantly, treatment of a triple-negative breast cancer mouse model with the NAD+ precursor nicotinamide mononucleotide (NMN) reduced tumour growth and did not impair the efficacy of chemotherapy drugs in vivo or in diverse cancer cell lines. Overall, these findings raise the possibility that NAD+ precursors could be a non-invasive strategy for maintaining ovarian function in cancer patients, with potential benefits in cancer therapy. Synopsis: Female fertility is impaired by chemotherapy in cancer patients. Fertility preservation relies on timely freezing of reproductive material prior to treatment, which is not always feasible. As chemo-induced infertility resembles ovarian ageing, we tested an agent that overcomes reproductive ageing. Boosting the nicotinamide adenine dinucleotide (NAD+) metabolome protected against chemotherapy-induced ovarian toxicity and female infertility. Effects on fertility were long-lasting, indicating long-term protection of the ovarian reserve. The efficacy of chemotherapy against tumour growth in mice was not impaired, indicating that ovarian function protection might not come at the cost of impaired cancer treatment. Female fertility is impaired by chemotherapy in cancer patients. Fertility preservation relies on timely freezing of reproductive material prior to treatment, which is not always feasible. As chemo-induced infertility resembles ovarian ageing, we tested an agent that overcomes reproductive ageing. [ABSTRACT FROM AUTHOR]

Background: Oocytes are a finite and non-renewable resource that are maintained in primordial follicle structures. The ovarian reserve is the totality of primordial follicles, present from birth, within the ovary and its establishment, size, and maintenance dictates the duration of the female reproductive lifespan. Understanding the cellular and molecular dynamics relevant to the establishment and maintenance of the reserve provides the first steps necessary for modulating both individual human and animal reproductive health as well as population dynamics. Summary: This review details the key stages of establishment and maintenance of the ovarian reserve, encompassing germ cell nest formation, germ cell nest breakdown, and primordial follicle formation and activation. Furthermore, we spotlight several formative single-cell sequencing studies that have significantly advanced our knowledge of novel molecular regulators of the ovarian reserve, which may improve our ability to modulate female reproductive lifespans. Key Messages: The application of single-cell sequencing to studies of ovarian development in mammals, especially when leveraging genetic and environmental models, offers significant insights into fertility and its regulation. Moreover, comparative studies looking at key stages in the development of the ovarian reserve across species has the potential to impact not just human fertility, but also conservation biology, invasive species management, and agriculture. [ABSTRACT FROM AUTHOR]