MEDICA@MUSC (Medical University of South Carolina)
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Pediatric Hearing Loss: Screening for Developmental Delays Among Children with Hearing Aids
No full textChildren with hearing impairments are at risk for developmental delay, and research has shown that children born with sensorineural hearing loss (SNHL) are at a higher risk for delays in motor, sensory, and social skills development. The literature points to an obvious impact of hearing loss on development, but also a lack of screening for this phenomenon beyond language development skills. A doctoral capstone project was conducted to pilot a process for the implementation of developmental screening for children with hearing aids (HAs), as well as subsequent therapy referrals and parent education, in collaboration with a hospital-based pediatric audiology department. The goals of the project included gaining an understanding of how the audiology department functions, identifying best practices for children with hearing impairments, and establishing effective interprofessional collaboration. This multi-faceted project consisted of screening and subsequent therapy referrals for 30 children with hearing aids, development of documentation strategies for audiologists, and the creation of resources and education for audiologists on scoring, interpreting results, and establishing proper referral criteria. Caregivers completed the Ages and Stages Questionnaire (ASQ) and Sensory Profile Two (SP2), two well-established developmental questionnaires that assess developmental milestones. Children were then referred to Occupational Therapy (OT), Physical Therapy (PT), or Developmental Pediatrics. Of the 30 children screened, all had bilateral or unilateral hearing aid devices due to SNHL, conductive hearing loss, or mixed hearing loss.Results indicated that out of the 30 children who received the ASQ/SP2, 14 (46.6%) qualified for at least one referral to services. The majority of referrals were made to OT (71.4%). Overall, qualitative data demonstrated perceived confidence in the screening process by pediatric audiologists, with 100% of survey participants reporting they “Strongly Agree or Agree” with feeling confident in administering developmental screeners in their clinical practice. In addition, 100% of participants reported they “Strongly Agree” that it is important and clinically relevant to administer developmental screeners to children with hearing impairments.This project has the potential to impact the future of Occupational Therapy and Audiology through increased interprofessional collaboration, ultimately resulting in improved quality of care. Furthermore, the overall impact of this project aims to recognize potential developmental delays earlier, leading to timely intervention that positively affects quality of life and improves overall outcomes for children with hearing loss
Maternal Physical and Mental Health in the State of South Carolina: Creating High-Quality Educational Materials
No full textThis capstone project, in collaboration with the Empowering Moms team at the Medical University of South Carolina, aimed to establish the foundation for a statewide occupational therapy initiative focused on maternal mental and physical health education as a preventative approach to addressing rising maternal mortality rates. The project involved assessing the needs of mothers, developing evidence-based educational materials, and compiling a comprehensive resource list to enhance access to information for mothers and community health partners (CHPs) across South Carolina. To support this initiative, a website and REDCap surveys were created to facilitate information dissemination and track outcomes. Embedded within the website, mothers and CHPs can schedule one-on-one or group informational sessions with a trained occupational therapist to learn more and ask questions. The community resources are categorized into the four regions of South Carolina for easy navigation. Community feedback indicates that the website is a valuable, user-friendly, and informative resource. Survey responses highlight increased awareness of maternal health topics, improved confidence in accessing community resources, and a greater understanding of occupational therapy’s role in maternal health
From Non-invasive to Metastatic Breast Cancer: Pathological Variation in Collagen Signatures within the Extracellular Microenvironment
No full textDuctal carcinoma in situ (DCIS) is not considered lethal, but its progression to invasive breast cancer (IBC) and subsequent metastasis to regional areas significantly increases mortality risk. The transition to IBC is associated with a marked increase in many collagens. Collagen post-translational regulation, especially proline hydroxylation (HYP), is crucial in modulating collagen structure and function, but post-translationally modified collagen domains remain largely unmapped in breast cancer. We hypothesize that the regulation of the collagen proteome evolves from non-invasive to metastatic breast cancer. Here, extracellular matrix (ECM)-targeted mass spectrometry imaging followed by high-resolution mass-accuracy proteomics was used to assess ECM proteomic changes from non-invasive to metastatic breast cancer. A comparison of DCIS specimens from recurrent and non-recurrent patients revealed a trend of reduced HYP collagen peptide profiles in recurrent patients. A significant decrease in HYP collagen peptide intensities was observed in recurrence events compared to patient-matched primary DCIS specimens, as well as between Black and White women. Individual peptides could discriminate between recurrence and primary DCIS. Comparative studies between pure DCIS, mixed DCIS-IBC, and pure IBC revealed distinct peptide signatures dependent on pathology, with proximity to IBC regions influencing ECM signatures of DCIS in mixed DCIS-IBC cases. In a multi-proteomic study of metastatic triple-negative breast cancer, many ECM proteins and remodelers were differentially expressed between the primary tumors, metastatic lymph nodes (LN), and benign LN. Specific collagen types were increased within the primary tumor, while others were similarly expressed across sites. Discrete ECM peptides had differential intensities between metastatic and benign LN. This dissertation defines ECM proteomic signatures spanning non-invasive to metastatic breast cancer
Improving Home Exercise Program Adherence in Stroke Survivors: Examining Influencing Factors and Developing Educational Resources for a Behavioral Intervention
No full textImproving Home Exercise Program Adherence in Stroke Survivors: Examining Influencing Factors and Developing Educational Resources for a Behavioral Intervention
Nearly 800,000 individuals experience a stroke annually in the United States and stroke often results in upper extremity functional limitation which can impact the individual’s ability to perform their activities of daily living. Because of this, home exercise programs are prescribed to facilitate rehabilitation; however, adherence is inadequate which ultimately impacts overall functional recovery. The purpose of this capstone is to enhance understanding of factors that influence home exercise program adherence and to improve upper extremity functional recovery post stroke through targeted educational modules and resources at a stroke recovery research center. The project goals were to investigate the effects of demographic and psychosocial factors on home exercise program adherence in stroke survivors through a research manuscript and to develop educational resources for a behavioral intervention to improve adherence. Factors associated with improved adherence to home exercise programs in stroke survivors included higher levels of digital health literacy, greater exercise self-efficacy, increased social support, veteran status, reduced anxiety, enhanced psychosocial functioning, effective communication after stroke, and a positive mood. These findings serve as the basis for the behavioral intervention modules that aim improve adherence, improve upper extremity functional outcomes, and facilitate long term behavioral changes in stroke survivors
The Impact of Diet-Induced Obesity on Cerebrovasculature Structure and Function
Get PDFAdequate cerebral perfusion is necessary to help the brain maintain a constant and steady state of nutrient delivery. Since the brain is highly metabolic, changes in the vasculature structure can impact perfusion levels and, therefore, reduce the ability of the brain to receive the support necessary for full functionality. Vascular dysfunction is a common comorbidity among obese individuals. Given the strong association between obesity and cognitive dysfunction, understanding the correlation between reduced cerebral perfusion and altered cerebrovascular structure is crucial. The overall hypothesis of this thesis originated after ample preliminary data, and states that diet-induced obesity reduces cerebral perfusion and alters the structural parameters of vasculature in the hippocampal region, contributing to cognitive decline.
To test our hypothesis, we assessed brain vasculature and perfusion levels in a murine model of diet-induced obesity following 6-24 weeks of either a standard or high-fat diet. We performed IHC leptin staining and utilized Zeiss 880 confocal microscopy to image the hippocampal region for quantification of branching points. Laser speckle imaging was used to measure perfusion levels, where changes were analyzed in PIMsoft software. After 24 weeks of diet in female mice, a high-fat diet significantly reduced perfusion in specific brain regions, with all regions showing a downward trend in perfusion levels. Male mice exhibited negative trends of perfusion levels in all regions after 24 weeks of a high-fat diet. A significantly higher number of branching points were found after 6 weeks of diet. However, after 24 weeks of diet, the standard diet mice maintained more branching points, suggesting that high-fat diet mice experience an unsustainable compensation mechanism that fails long term, while healthy mice sustain consistent levels
Resource Toolkit Development for Mental Health Awareness in School-Aged Children
Get PDFIntroduction: Mental health challenges are on the rise, and school-aged children often lack mental health services and education at an early age, which can lead to mental illness. Therefore, it is important to increase awareness of mental health challenges in school-aged children by educating individuals to reduce the stigma. Providing school and community-based resources to improve overall health and well-being is essential to combat the rise in mental illness in our communities.
Methods: A quality improvement (QI) design for product development and education was aimed at addressing this rising problem. The needs assessment results, current literature, evidence-based practices, and conceptual frameworks guided the design. Participants included individuals who work with or have school-aged children, community stakeholders, resource toolkit users, and educational in-service attendees. The procedures for the QI project consisted of developing community partnerships, a resource toolkit available to local communities, and educating others on mental health. Data was collected via surveys to assess user experience after the use of the resource toolkit, as well as comparisons of pre- and post-test knowledge and confidence gains after an educational in-service.
Results: The data showed positive results related to user experience, with participants finding the developed resource toolkit to be useful and easy to use. Data also shows an increase in both the knowledge and confidence of attendees following the education in-service. There were higher knowledge changes and confidence gains when comparing pre- and post-surveys. Limitations of the QI project included limited time, sample size, and resources available.
Conclusion: This project demonstrated a positive impact on the community by addressing the rising mental health crisis by providing education to reduce the stigma. The project development and education can help reduce the negative effects related to mental illness and reduce the ripple effect that mental illness can cause. Overall, the impact of resources provided allows individuals to promote the health and wellness of school-aged children to improve their quality of life
Occupational Therapy Fellowship Curriculum Design: A Framework and Curriculum Mapping
No full textObjective. There is little published research on occupational therapy (OT) fellowships and varying levels of understanding around fellowships. The purposes of this IRB-exempt capstone were to identify stakeholder perception of OT fellowships, create a neurologic OT fellowship to bridge the gap in access to this training in the Southeast, and apply a conceptual framework during development. Methods. Anonymous surveys and semi-structured interviews were used to identify stakeholder needs for the curriculum. Methods focused on curriculum outline, development of one educational lesson, and incorporating formative and summative assessments. Five volunteers rated the module on usability and overall experience. The curriculum was rated according to national standards to determine whether it meets accreditation objectives. Finally, curriculum mapping was completed with the chosen conceptual framework. Results. 82.1% of the 123 OT/OTS respondents reported some knowledge of OT fellowships but only 18.9% had a thorough understanding. Six expert clinicians and two directors were also included as stakeholders. Across all stakeholder groups, mentorship, exposure to multiple settings and specialty-specific coursework were the most valuable components. The curriculum met 95% of fellowship learning objectives and volunteers had an overall positive response to the lesson across five of six user experience subscales. Conclusion. Knowledge of fellowships varies among OTs and OT students. There seems to be consensus among stakeholders that mentorship, exposure to multiple settings, and specialty-focused didactics are key. This project will add to the growing body of evidence on OT fellowships and their development, design, and theoretical frameworks
Genetics and Mechanisms Underlying Karyokinesis and Cytokinesis in Cardiomyocytes
No full textThe mammalian adult heart has limited ability to regenerate, partly because most cardiomyocytes (CMs) are polyploid. The frequency of potentially regenerative diploid CMs in the adult heart is determined by multiple polymorphic genes. By identifying these genes, it might be possible to clarify mechanisms that influence whether CMs entering the cell cycle can complete it or instead fail during karyokinesis or cytokinesis.
BALB/cJ and BALB/cByJ mice are highly related sister strains that diverge substantially in mononuclear CM frequency and CM ploidy. Our evidence suggests that the difference in CM ploidy is an autosomal trait, whereas the variation in mononuclear CM frequency is X-linked. Additionally, we identified a large deletion in the Cyth1 gene that arose uniquely in BALB/cByJ mice, creating a null allele. The deletion also results in ectopic transcription of the downstream gene Dnah17, although this transcript is unlikely to encode a protein. By evaluating the natural null allele from BALB/cByJ and an engineered knockout allele in the C57BL/6J background, we determined that absence of Cyth1 alone does not influence CM ploidy. The ready availability of BALB/cByJ mice may be helpful to other investigations of Cyth1 in other biological processes.
A genome-wide association study of the BXD mouse strains implicated a locus on Chr 3 that influences the percentage of mononuclear CMs. My analysis confirmed that Spg20, located within the locus, is more highly expressed in C57BL/6J compared to DBA/2J mice. A SNP in the 3’ untranslated sequence (rs30203612) in DBA/2J mice may underlie the differential expression. The Spg20 protein (Spartin) is known in other cell types to colocalize with the ESCRT III protein Ist1 at the midbody during the cytokinesis, where it regulates the microtubule-severing protein (Spastin). Immunostaining showed that Spartin is recruited to the midbody in primary neonatal CMs during cytokinesis. This work points to a potential molecular mechanism linking Spartin with the ESCRT complex in cytokinesis, influencing CM cell cycle completion.
In addition to genetic factors, we also found that the corncob bedding used in mouse cages affects CM phenotype. In summary, these research findings contribute to a better understanding of karyokinesis and cytokinesis in CMs, paving the way for heart regeneration
The E3 Ubiquitin Ligase ARIH-1 and its Role in Chemoresponse in TNBC
No full textIn comparison to other subtypes, triple-negative breast cancer (TNBC) has limited treatment options due to its heterogeneous nature and lack of therapeutic targets compared to non-TNBC. Accounting for 15-20% of all breast cancers, TNBC is characterized by its lack of expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). The standard of care is neoadjuvant chemotherapy, followed by surgery if applicable and adjuvant chemotherapy. The effectiveness of this treatment course is limited due to its severe side-effects such as cardiotoxicity and chemoresistance. The development of resistance to chemotherapy is more common in TNBC than in other subtypes and its underlying mechanism is still elusive.
We aim to define the mechanisms through which the E3 ubiquitin ligase ARIH-1 impacts chemoresponse in TNBC, as breast cancer (BC) patient data show higher ARIH-1 transcript levels correlate with worse survival. We have previously identified a novel role for ARIH-1 in the epithelial to mesenchymal transition (EMT), tumor initiation, and metastatic progression of TNBC. EMT, a process that is aberrantly activated in cancer, is associated with increased cell migration, invasion, and the acquisition of cancer stem cell (CSC) traits that enhance chemoresistance. Based on these findings, we looked at the impact of ARIH-1 in response to chemotherapy.
We assessed ARIH-1 expression in the Doxorubicin-resistant cell line of our TNBC MDA-MB-231 cells model, showing ARIH-1 is upregulated in these cells at the transcript and protein level. To test the impact of ARIH-1 on cancer cell viability, we generated MDA-MB-231 TNBC cells overexpressing (OE) or silencing (KD) ARIH-1. We show that ARIH-1 silencing increases response to chemotherapy treatment with Doxorubicin, a DNA-damaging anthracycline. To assess the biochemical mechanism linking ARIH-1 to chemoresistance, we utilized miniTurboID proximity labeling method to identify and test novel targets of ARIH-1 potentially related to chemoresistance or DNA damage response pathways. Here, we identified topoisomerase II-alpha (TOP2A), an enzyme involved in DNA topology regulation. Cycloheximide chase assay successfully demonstrated TOP2A stability is regulated by ARIH-1-mediated proteasomal degradation and silencing ARIH-1 improves TOP2A’s DNA decatenation ability when compared to control. Together, we validate this target as a candidate substrate of ARIH-1 that may be impacting chemotherapy sensitivity
Waring Library Society Newsletter, Summer 2024
Get PDFIn this issue, Waring Library Society President Dr. Robert Ball reflects on the legacy of MUSC\u27s founders; JoAnn Zeise discusses the construction of the Waring Historical Library; Anna Marie Schuldt announces the fall 2024 SHC Noon Lectures; and David Adams provides insight into the fundraising process for the Waring Historical Library.https://medica-musc.researchcommons.org/wls-newsletters/1009/thumbnail.jp