The field of audiology as a collection of auditory science knowledge, research, and clinical methods, technologies, and practices has seen great changes. A deeper understanding of psychological, cognitive, and behavioural interactions has led to a growing range of variables of interest to measure and track in diagnostic and rehabilitative processes. Technology-led changes to clinical practices, including teleaudiology, have heralded a call to action in order to recognise the role and impact of autonomy and agency on clinical practice, engagement, and outcomes. Advances in and new information on loudness models, tinnitus, psychoacoustics, deep neural networks, machine learning, predictive and adaptive algorithms, and PREMs/PROMs have enabled innovations in technology to revolutionise clinical principles and practices for the following: (i) assessment, (ii) fitting and programming of hearing devices, and (iii) rehabilitation. This narrative review will consider how the rise of teleaudiology as a growing and increasingly fundamental element of contemporary adult audiological practice has affected the principles and practices of audiology based on a new era of knowledge and capability. What areas of knowledge have grown? How has new knowledge shifted the priorities in clinical audiology? What technological innovations have been combined with these to change clinical practices? Above all, where is hearing loss now consequently positioned in its journey as a field of health and medicine?

The Interprofessional Research Design course uses authentic learning pedagogy to bring together students from different education tracks (PhD, MD, MD/PhD training) to engage in interprofessional collaborative skills toward completion of a capstone project, a National Health Institutes (NIH) R21-style grant proposal. The course, underpinned by principles of team science, begins with a leadership training workshop to introduce students to effective leadership and teamwork strategies for interprofessional team environments. We used several assessments during the course to monitor leadership and team dynamics. We analyzed three assessments (leadership self-efficacy testing, iterative team contracts and reflective essays) to better understand students\' learning experiences. Self-efficacy testing was administered before leadership training (pre) and at the end of the course (post-then); scores were analyzed using a repeated repeated measures ANOVA. Iterative team contracts were analyzed qualitatively using both deductive and descriptive methods. Reflective essays were analyzed using a general inductive approach. Nine teams of 32 students (23 MD; 9 PhD) participated in the class over 2017-2018. Self-efficacy testing using post-then timing to control for response shift showed a statistically significant increase in self-efficacy across all measures. Deductive qualitative analysis of iterative contracting showed evidence of team processes which support successful team performance; and descriptive analysis mapped productive behaviors. In reflective essays, seven of the nine teams collectively described their experiences positively; e.g., themes included empathizing with group members, sophisticated communication and collaborative workflow/styles. For negative experiences, themes were related to basic communication, poor integration and the theory-practice gap of leadership training. These findings demonstrate the usefulness of an authentic learning pedagogy focused on teaching the practice of team science.

Identifying the mechanisms of action of existing and novel drugs is essential for the development of new compounds for therapeutic and commercial use. Here we provide a technique to identify these mechanisms through isolating mutant cell lines that show resistance to drug-induced phenotypes using Dictyostelium discoideum REMI libraries. This approach provides a robust and rapid chemical-genetic screening technique that enables an unbiased approach to identify proteins and molecular pathways that control drug sensitivity. Mutations that result in drug resistance often occur in target proteins thus identifying the specific protein targets for drugs and bioactive natural products. Following the identification of a list of putative molecular targets user selected compound targets can be analyzed to confirm and validate direct inhibitory effects.

Cardiovascular diseases are considered the leading cause of mortality globally; even with low mortality in dogs, such diseases are described in the same way in companion animals and humans. This study aimed to devise an effective decellularization protocol for the canine myocardium through the association of physical, chemical, and enzymatic methods, assessing resultant alterations in the myocardial extracellular matrix to obtain a suitable scaffold. Two canine hearts were collected; the samples were sectioned into ±1 cm2 fragments, washed in distilled water and 1× PBS solution, and followed by treatment under four distinct decellularization protocols. Sodium Dodecyl Sulfate (SDS) 1% 7 days + Triton X-100 1% for 48 h (Protocol I); Sodium Dodecyl Sulfate (SDS) 1% 5 days + Triton X-100 1% for 48 h (Protocol II); Trypsin 0.05% for 1 h at 36 °C + freezing -80 °C overnight + Sodium Dodecyl Sulfate (SDS) 1% for 3 days, Triton-X-100 for 48 h hours (Protocol III); 0.05% trypsin for 1 h at 36 °C + freezing at -80 °C overnight + 1% Sodium Dodecyl Sulfate (SDS) for 2 days + 1% Triton-X-100 for 24 h (Protocol IV). After analysis, Protocols I and II showed the removal of cellular content and preservation of extracellular matrix (ECM) contents, unlike Protocols III and IV, which retracted the ECM and removed essential elements of the matrix. In theory, although Protocols I and II have similar results, Protocol II stands out for the preservation of the architecture and components of the extracellular matrix, along with reduced exposure time to reagents, making it the recommended protocol for the development of a canine myocardial scaffold.

Academic medical centers and university extension programs remain underdeveloped collaborators, despite the complementary objectives between translational science and extension. This case study details the creation of a nationally unique interprofessional organizational structure between the University of Missouri (MU) Office of Extension and Engagement (MU Extension) and the MU School of Medicine to accelerate statewide reach of research and education discoveries using high-touch community health approaches. This article describes specific strategies used to systematically plan for: 1) creation and operation of the new structure, 2) routinization and institutionalizing the work, and 3) sustainability. We further outline challenges and next steps. The development of the backbone organization office of Health Outreach Policy and Education (HOPE) brings together the interprofessional expertise of five units with a common agenda to advance mutually reinforcing activities. HOPE is poised to make significant contributions to amplify MU\'s land grant mission, garner additional grant funding, and advance the health of Missourians.

Extracellular Matrix (ECM) scaffolds and biomaterials have been widely used for decades across a variety of diverse clinical applications and have been implanted in millions of patients worldwide. ECM-based biomaterials have been especially successful in soft tissue repair applications but their utility in other clinical applications such as for regeneration of bone or neural tissue is less well understood. The beneficial healing outcome with the use of ECM biomaterials is the result of their biocompatibility, their biophysical properties and their ability to modify cell behavior after injury. As a consequence of successful clinical outcomes, there has been motivation for the development of next-generation formulations of ECM materials ranging from hydrogels, bioinks, powders, to whole organ or tissue scaffolds. The continued development of novel ECM formulations as well as active research interest in these materials ensures a wealth of possibilities for future clinical translation and innovation in regenerative medicine. The clinical translation of next generation formulations ECM scaffolds faces predictable challenges such as manufacturing, manageable regulatory pathways, surgical implantation, and the cost required to address these challenges. The current status of ECM-based biomaterials, including clinical translation, novel formulations and therapies currently under development, and the challenges that limit clinical translation of ECM biomaterials are reviewed herein.

In the 1980s, Orion Pharma, then a mid-ranking Nordic area pharmaceutical company, established a drug development programme on the inhibition of catechol O-methyltransferase (COMT). This enzyme, which plays an important role in the inactivation of catecholamine neurotransmitters and drugs with a catechol structure, thus came under consideration as a target in the innovative translational and clinical programme we describe in this historical review. The starting point was the conjecture that a peripherally acting COMT inhibitor might improve entry of levodopa into the brain. This had potentially significant implications for the medical treatment of Parkinson\'s disease (PD). The rationale was that more efficient delivery of levodopa to the brain might allow the high therapeutic doses of levodopa to be reduced and the dose interval to be extended. Elucidation of structure-activity relations paved the way for the discovery and development of entacapone, a 5-nitrocatechol that was a potent and highly specific inhibitor of COMT. Experience in phase III clinical trials established that entacapone, used as an adjunct to regular or controlled-release levodopa preparations (also including a peripherally acting dopa-decarboxylase inhibitor), increased ON-time and reduced OFF-time and improved clinical condition in patients with PD experiencing wearing-off, often with a reduced daily levodopa dose. Several of these studies also identified that entacapone improved patients\' quality of life and was cost-effective. Subsequently, entacapone has been amalgamated into a triple-combination preparation (Stalevo®) with levodopa and carbidopa to create a flexible and convenient drug therapy for patients with PD who have end-of-dose motor fluctuations not stabilised on levodopa/dopa-decarboxylase inhibitor treatment. This review offers a historical perspective on a successful programme of drug development by researchers who played central roles in the progress from exploratory hypothesis to registered pharmaceutical product.

Silk and silk derivatives have emerged as a possible alternative in surgical device development, offering mechanical strength, biocompatibility, and environmental sustainability. Through a systematic review following PRISMA guidelines, this study evaluated silk fibroin\'s application across pre-clinical and clinical settings, focusing on its role as screws and plates for osteofixation. A comprehensive search yielded 245 studies, with 33 subjected to full-text review and 15 ultimately included for qualitative analysis. The findings underscore silk fibroin\'s superior properties, including its tunable degradation rates and ability to be functionalized with therapeutic agents. In vivo and in vitro studies demonstrated its efficacy in enhancing bone healing, offering improved outcomes in osteofixation, particularly for craniofacial defects. Silk fibroin\'s remarkable attributes in biodegradation and drug release capabilities underscore its potential to enhance patient care. Ultimately, silk fibroin\'s integration into surgical practices promises a revolution in patient outcomes and environmental sustainability. Its versatility, coupled with the continuous progress in fabrication techniques, signals a promising horizon for its widespread acceptance in the medical field, potentially establishing a new benchmark in surgical treatment. Further research is expected to solidify the transition of silk products from basic science to patient care, paving the way for widespread use in various surgical applications.

N6-methyladenosine (m6A) modification, a eukaryotic messenger RNA modification catalyzed by methyltransferase-like 3 (METTL3), plays a pivotal role in stem cell fate determination. Calvarial bone development and maintenance are orchestrated by the cranial sutures. Cathepsin K (CTSK)-positive calvarial stem cells (CSCs) contribute to mice calvarial ossification. However, the role of m6A modification in regulating Ctsk+ lineage cells during calvarial development remains elusive. Here, we showed that METTL3 was colocalized with cranial nonosteoclastic Ctsk+ lineage cells, which were also associated with GLI1 expression. During neonatal development, depletion of Mettl3 in the Ctsk+ lineage cells delayed suture formation and decreased mineralization. During adulthood maintenance, loss of Mettl3 in the Ctsk+ lineage cells impaired calvarial bone formation, which was featured by the increased bone porosity, enhanced bone marrow cavity, and decreased number of osteocytes with the less-developed cellular outline. The analysis of methylated RNA immunoprecipitation sequencing and RNA sequencing data indicated that loss of METTL3 reduced Hedgehog (Hh) signaling pathway. Restoration of Hh signaling pathway by crossing Sufufl/+ alleles or by local administration of SAG21 partially rescued the abnormity. Our data indicate that METTL3 modulates Ctsk+ lineage cells supporting calvarial bone formation by regulating the Hh signaling pathway, providing new insights for clinical treatment of skull vault osseous diseases.

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