Browsing by Author "McNulty, Margaret A."

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    Abnormal epiphyseal development in a feline model of Sandhoff disease
    (Wiley, 2020-12) McNulty, Margaret A.; Prevatt, Patricia B.; Nussbaum, Elizabeth R.; Randle, Ashley N.; Johnson, Aime K.; Hudson, Judith A.; Gray-Edwards, Heather L.; Sena-Esteves, Miguel; Martin, Douglas R.; Carlson, Cathy S.; Anatomy, Cell Biology and Physiology, School of Medicine
    Sandhoff disease (SD) is caused by decreased function of the enzyme β-N-acetylhexosaminidase, resulting in accumulation of GM2 ganglioside in tissues. Neural tissue is primarily affected and individuals with the infantile form of the disease generally do not survive beyond 4 years of age. Current treatments address neurometabolic deficits to improve lifespan, however, this extended lifespan allows clinical disease to become manifest in other tissues, including the musculoskeletal system. The impact of SD on bone and joint tissues has yet to be fully determined. In a feline model of infantile SD, animals were treated by intracranial injection of adeno-associated virus vectors to supply the central nervous system with corrective levels of hexosaminidase, resulting in a twofold to threefold increase in lifespan. As treated animals aged, signs of musculoskeletal disease were identified. The present study characterized bone and joint lesions from affected cats using micro-computed tomography and histology. All affected cats had similar lesions, whether or not they were treated. SD cats displayed a significant reduction in metaphyseal trabecular bone and markedly abnormal size and shape of epiphyses. Abnormalities increased in severity with age and appear to be due to alteration in the function of chondrocytes within epiphyseal cartilage, particularly the articular-epiphyseal complex. Older cats developed secondary osteoarthritic changes. The changes identified are similar to those seen in humans with mucopolysaccharidoses. Statement of clinical significance: the lesions identified will have significant implications on the quality of life of individuals whose lifespans are extended due to treatments for the primary neurological effects of SD.
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    An Anatomy Pre-Course Predicts Student Performance in a Professional Veterinary Anatomy Curriculum
    (AAVMC, 2018) McNulty, Margaret A.; Lazarus, Michelle D.; Anatomy and Cell Biology, IU School of Medicine
    Little to no correlation has been identified between previous related undergraduate coursework or outcomes on standardized tests and performance in a veterinary curriculum, including anatomy coursework. Therefore, a relatively simplistic method to predict student performance before entrance would be advantageous to many. The purpose of this study was to evaluate whether there is a correlation between performance in a veterinary anatomy pre-course and subsequent performance within a professional anatomy curriculum. Incoming first-year veterinary students at the Louisiana State University School of Veterinary Medicine were asked to participate in a free weeklong pre-course, before the start of the semester. The pre-course covered the musculoskeletal anatomy of the canine thoracic limb using dissection-based methods. Student performance, as evaluated by test grades in the pre-course, did indeed correlate with test grades in professional veterinary anatomy courses. A significant and positive correlation was identified between pre-course final exam performance and performance on examinations in each of 3 professional anatomy courses. Qualitative analyses of student comments pertaining to their experience within the pre-course indicated differences in the perceived benefits of the pre-course between high-, middle-, and low-performing students. These varied perceptions may provide predictive feedback as well as guidance for supporting lower performing students. Together, these results indicate that performance in a weeklong pre-course covering only a small portion of canine anatomy is a strong predictor of performance within a professional anatomy curriculum. In addition, the pre-course differentially affected student perceptions of their learning experience.
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    Anatomy Preparedness in Medical Education: Determining and Building Sufficient Preparedness in Professional Anatomy Courses
    (2023-08) Balle, Megan C.; McNulty, Margaret A.; Agosto, Elizabeth R.; Byram, Jessica N.; Graunke, Steven S.; Magee, Paula A.; Williams, James C.
    Widely accepted as a foundational course within health professions education, anatomy is often taken at the beginning of the health professional curriculum and students are expected to be prepared for the rigors of the course. Anatomy preparedness, evaluated in this study, has been defined as matriculating into a graduate or professional anatomy course with an adequate foundation in basic anatomy knowledge. In a mixed-methods study, pre-requisite syllabi of physician assistant students were analyzed via deductive content analysis to explore common traits within each group. The top and bottom 10% performing students were invited to participate in semi-structured interviews, n=5 participated. Additionally, correlation analyses were used to determine whether performance on a basic anatomy pre-quiz could aid in identifying allied health students with the potential to struggle in a professional anatomy course. A post-course survey was given to determine in which anatomy topics students felt underprepared upon matriculation, prior anatomy experience, feelings of preparedness, and anatomy pre-requisite recommendation. Finally, a pre-matriculation program targeting under-represented in medicine (URiM) students and those at-risk for failure in the medical program was developed. Correlation analyses were used to determine if there was a relationship between performance in the pre-matriculation program and the medical anatomy course. The same post-course survey was administered and focus groups were conducted; transcripts were analyzed via deductive content analysis. Syllabi traits critical to student success included exposure to specimens/prosections, practical exams, and supply of study resources; interviewees also perceived these traits to be important. Twenty-question pre-quiz scores significantly and positively correlated with student performance in their professional anatomy course. Students reported feeling deficient in anatomicomedical terminology and the nervous system. The pre-matriculation program was a success, with students performing at or above average within their cohort and compared to other URiM students. Both allied health and pre-matriculation students recommended taking anatomy prior to professional school. As seen in this study, students are capable of success with the proper resources and support. Furthermore, allied health and medical students recognized the importance of anatomy preparedness for success in health professional anatomy coursework and their openness to resources aimed at supporting their success.
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    Approaches to Improve the Structure and Function of the Skeleton in Chronic Kidney Disease
    (2022-03) Swallow, Elizabeth Anne; Allen, Matthew R.; McNulty, Margaret A.; Moe, Sharon M.; Wallace, Joseph M.
    Chronic kidney disease (CKD) currently affects ~37 million Americans and causes substantially increased risk of skeletal fracture and fracture-related mortality. Current methods to treat CKD-related bone loss remain alarmingly ineffective. Skeletal fragility in CKD is predominately driven by deteriorations in cortical bone, highlighted by significant cortical porosity development. It is hypothesized that cortical porosity is largely driven by chronically high levels of parathyroid hormone (PTH), which alters the balance of bone remodeling in favor of rampant osteoclast activity and bone resorption. Restricting cortical bone deterioration and the development of cortical pores is likely essential to improve CKD patients’ bone health and reduce their fracture risk. The goal of this series of studies was to answer the following key questions: (1) to what degree do bisphosphonates, an approved pharmacological agent used in metabolic bone disease, accumulate in the skeleton of animals with CKD; (2) can smaller and more frequent doses of bisphosphonates alter skeletal accumulation and improve cortical architecture and the mechanical integrity of bone; (3) can non-bisphosphonate pharmacological interventions more specifically affect cortical bone deterioration. Utilizing epi-fluorescence and two-photon microscopy, our results show that bisphosphonates accumulate more in rats with renal impairment and fractionating bisphosphonates lowered skeletal accumulation irrespective of disease state. Further, studies in both rat and mouse models of CKD demonstrated different bisphosphonate treatments alone do not recover declines in cortical microarchitecture or mechanical properties in CKD. These findings demonstrate that a single intervention is not sufficient in managing CKD-induced bone alterations. Utilizing individual pore tracking analysis, we demonstrated cortical pores can be modulated with therapeutic interventions and can infill, despite the presence of CKD. Potent suppression of PTH led to significant pore infilling while more subtle reductions in PTH, via a calcimimetic, had less striking effects on bone. Calcimimetics mitigated cortical microarchitecture deterioration and reduced the rate of cortical pore expansion. Overall, these findings highlight the importance of PTH management for treating cortical deterioration in CKD. Although bisphosphonates can be utilized in ways that reduce skeletal accumulation, they appear to need co-therapies to reduce skeletal fragility associated with CKD.
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    Breaking barriers: The landscape of human and veterinary medical anatomy education and the potential for collaboration
    (American Association for Anatomy, 2021-07) McNulty, Margaret A.; Mussell, Jason C.; Lufler, Rebecca S.; Anatomy and Cell Biology, School of Medicine
    Despite human (HUM) and veterinary (VET) medical institutions sharing the goal of educating future clinicians, there is little collaboration between them regarding curricular and pedagogical practices during the preclinical/basic science training years. This may be, at least in part, due to a lack of understanding of each type of curriculum. This study presents data about curricula, student populations, pedagogical methodologies applied, and anatomy educators' training at both HUM and VET institutions. Preclinical curricula, admissions criteria, and student demographics were analyzed for 21 institutions in the United States having both HUM and VET schools. This dataset was augmented by a questionnaire sent to anatomists internationally, detailing anatomy curricula, pedagogies applied, and anatomy educators' training. Many curricular similarities between both training programs were identified, including anatomy education experiences. However, VET programs were found to include more preclinical coursework than HUM programs. Students who matriculate to VET or HUM schools have similar academic records, including prerequisite coursework and grade point average. Median HUM class size was significantly larger, and the percentage of women enrolled in VET institutions was significantly higher. Training of anatomy educators was identical with one exception: VET educators are far more likely to hold a clinical degree. This study elucidates the substantial similarities between VET and HUM programs, particularly in anatomy education, underscoring the potential for collaboration between both types of programs in areas such as interprofessional education, bioethics, zoonotic disease management, and postgraduate training.
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    Characterizing Femoral Structure of the Ts66Yah Mouse Model of Down Syndrome
    (2023-08) Sloan, Kourtney; Roper, Randall J.; Li, Jiliang; McNulty, Margaret A.; Picard, Christine J.
    Down syndrome (DS) is caused by the partial or complete trisomy of human chromosome 21 (Hsa21) and can result in skeletal deficits, including lower bone mineral density (BMD) and increased risk of fracture and osteoporosis or osteopenia earlier than the general population. Mouse models of DS have been developed to understand the genetic mechanisms resulting in these phenotypes, but models differ due to the complex genetic nature of DS and differing genome structures between humans and mice. Ts65Dn mice have been a popular model of DS as they contain ~50% of Hsa21 orthologous genes on a freely segregating minichromosome, but there is speculation that the phenotypes are exaggerated by non-Hsa21 orthologous trisomic genes also present. To address this issue, the Ts66Yah mouse model was developed to remove the non-Hsa21 orthologous trisomic genes. In this study, male and female Ts66Yah mouse femurs were evaluated during bone accrual and peak bone mass to investigate structural differences using micro-computed tomography. Additionally, the role of trisomic Dyrk1a, a Hsa21 gene previously linked to bone deficits in Ts65Dn mice, was evaluated through genetic and pharmacological means in Ts66Yah femurs at postnatal day 36. Ts66Yah mice were found to have little or no trabecular deficits at any age evaluated, but sex-dependent cortical deficits were present at all ages investigated. Reducing Dyrk1a copy number in Ts66Yah mice significantly improved cortical deficits but did not return cortical bone to euploid levels. Pharmacological treatment with DYRK1A inhibitor L21 was confounded by multiple variables, making it difficult to draw conclusions about DYRK1A inhibition in this manner. Overall, these results indicate trabecular deficits associated with Ts65Dn mice may be due to the non-Hsa21 orthologous trisomic genes, and more Hsa21 orthologous trisomic genes are necessary to produce trabecular deficits in DS model mice. As more mouse models of DS are developed, multiple models need to be assessed to accurately define DS-associated phenotypes and test potential treatments.
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    Determining baseline anatomy knowledge among professional allied health students
    (American Association for Anatomy, 2023-03) Fagalde, Megan C.; McNulty, Margaret A.; Anatomy, Cell Biology and Physiology, School of Medicine
    Health professional students often struggle with anatomy coursework despite undergraduate coursework in anatomy. Educators must identify early on whether students may struggle in order to target remediation. The purpose of the study was to elucidate whether an assessment tool administered before the start of a professional anatomy course correlated with allied health students' course performance. Students over four years were given a quiz covering anatomy knowledge they were expected to know upon matriculation to their professional program. A supplemental data form was administered at the course's conclusion to identify prior anatomy experience and topics in which students felt deficient. Pre-quiz scores significantly correlated with examination performance throughout the course. Students reported feeling most deficient in neurobiology (54.9%) and anatomy terminology (39.1%). Videos were created to target these deficient knowledge areas; students who watched the videos did better in course assessments than those who did not. Most respondents (98.0%) recommended students take an undergraduate anatomy course prior to starting a health professional program. These results indicate that a quiz assessing anatomy knowledge among matriculating students may identify students with the potential to struggle in a professional anatomy course early on. Responses outlined areas in which students felt deficient, which allows educators to target topics early with intervention tools such as the review videos in this study. Finally, most respondents strongly recommended undergraduate coursework in anatomy prior to starting a professional health program, which outlines students' recognition that a solid foundation in anatomical knowledge is important to success in professional programs.
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    Experiences of Residency Program Directors in Their Roles: Exploring Well-Being Through Burnout and Engagement
    (2022-11) Robertson, Kyle A.; Byram, Jessica N.; Hayes, Cleveland; Agosto, Elizabeth R.; McNulty, Margaret A.; Organ, Jason M.
    Recent literature on well-being of physicians in general, and residency program directors (PD) specifically, has demonstrated those meeting the criteria of burnout reaching almost 50% in physicians, and 20-30% in PDs. However, few studies have explored engagement, or the positive or meaningful aspects, in physicians and no studies have explored engagement in the PD and Assistant PD community. Therefore, this study employed a qualitative approach to explore the experiences of PDs and APDs as they encountered burnout, engagement, and every combination in between through their multifaceted, roles, responsibilities, and tasks embedded in their institutional context and personal lives. Phase 1 participants (n=3) included two PDs and one APD from Indiana University School of Medicine (IUSM). Participants in Phase 1 took part in three semi-structured interviews at 6-month intervals, and direct observations in their clinical, administrative, and education roles. Phase 2 participants (n=5) were PDs from IUSM who completed a single semi-structured interview based on preliminary results and exploration of Phase 1 participants’ experiences. Interviews and field notes from observations were analyzed using inductive thematic analysis, followed by a deductive application of Job Demands-Resources (JD-R) theory. Document analysis was incorporated to add context, understanding, and a rich description of the participants’ experiences. This study found multiple sub-themes situated within four major themes: It Takes a Village, Integration of the “Hats” They Wear, Motivation and the Meaning of Their Career, and Coping. Exploring the sub-themes to JD-R theory allowed contextualization of how job demands, job resources, personal resources, absence of resources, job crafting, recovery, self-undermining, and strain, interact to add context, nuance, and broader conceptualization of how PD and APD experienced their multifaceted roles. This study provides a rich description of the experiences of PDs and APDs embedded in their social context of roles, tasks, and responsibilities. These results indicated that understanding how the individual experiences their job demands as they interact with their experiences of job and personal resources, and how the individual proactively engages with their environment through job crafting and recovery enables for a nuanced appreciation of engagement and burnout.
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    FGF21, not GCN2, influences bone morphology due to dietary protein restrictions
    (Elsevier, 2020- 06) McNulty, Margaret A.; Goupil, Brad A.; Albarado, Diana C.; Castaño-Martinez, Teresa; Ambrosi, Thomas H.; Puh, Spela; Schulz, Tim J.; Schürmann, Annette; Morrison, Christopher D.; Laeger, Thomas; Anatomy and Cell Biology, School of Medicine
    Background Dietary protein restriction is emerging as an alternative approach to treat obesity and glucose intolerance because it markedly increases plasma fibroblast growth factor 21 (FGF21) concentrations. Similarly, dietary restriction of methionine is known to mimic metabolic effects of energy and protein restriction with FGF21 as a required mechanism. However, dietary protein has been shown to be required for normal bone growth, though there is conflicting evidence as to the influence of dietary protein restriction on bone remodeling. The purpose of the current study was to evaluate the effect of dietary protein and methionine restriction on bone in lean and obese mice, and clarify whether FGF21 and general control nonderepressible 2 (GCN2) kinase, that are part of a novel endocrine pathway implicated in the detection of protein restriction, influence the effect of dietary protein restriction on bone. Methods Adult wild-type (WT) or Fgf21 KO mice were fed a normal protein (18 kcal%; CON) or low protein (4 kcal%; LP) diet for 2 or 27 weeks. In addition, adult WT or Gcn2 KO mice were fed a CON or LP diet for 27 weeks. Young New Zealand obese (NZO) mice were placed on high-fat diets that provided protein at control (16 kcal%; CON), low levels (4 kcal%) in a high-carbohydrate (LP/HC) or high-fat (LP/HF) regimen, or on high-fat diets (protein, 16 kcal%) that provided methionine at control (0.86%; CON-MR) or low levels (0.17%; MR) for up to 9 weeks. Long bones from the hind limbs of these mice were collected and evaluated with micro-computed tomography (μCT) for changes in trabecular and cortical architecture and mass. Results In WT mice the 27-week LP diet significantly reduced cortical bone, and this effect was enhanced by deletion of Fgf21 but not Gcn2. This decrease in bone did not appear after 2 weeks on the LP diet. In addition, Fgf21 KO mice had significantly less bone than their WT counterparts. In obese NZO mice dietary protein and methionine restriction altered bone architecture. The changes were mediated by FGF21 due to methionine restriction in the presence of cystine, which did not increase plasma FGF21 levels and did not affect bone architecture. Conclusions This study provides direct evidence of a reduction in bone following long-term dietary protein restriction in a mouse model, effects that appear to be mediated by FGF21.
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    The glass ceiling thickens: the impact of COVID-19 on academic medicine faculty in the United States
    (Taylor & Francis, 2022) Lufler, Rebecca S.; McNulty, Margaret A.; Anatomy, Cell Biology and Physiology, School of Medicine
    The inequities faced by women in academic Medicine before the COVID-19 pandemic are well established. However, there is little formal data regarding exactly how the pandemic has affected faculty. This cross-sectional study investigated the impact of the pandemic on responsibilities at home, work, and mental health according to gender identification, faculty rank, and faculty appointment. In February 2021, an online questionnaire was broadly distributed to academic medicine faculty. Respondents were asked to provide demographic data, answer questions about their responsibilities at home and work, mental health, and how the pandemic has influenced these. Respondents were also asked to document what their institution(s) can do to help faculty through the pandemic. Responses were analyzed via Pearson's chi-square tests and thematic analysis. Women faculty were more likely to be responsible for the care of others (70%, p = 0.014), and the impact was negative, especially for early career faculty (p = 0.019). Productivity in research, teaching, and clinical practice were negatively impacted, with women feeling this in clinical practice (p = 0.005), increased teaching load (p = 0.042), and inadequate work environment (p = 0.013). In the areas of self-care and mental health, women (p < 0.001), early career-faculty (p < 0.001), and clinical faculty (p = 0.029) were more negatively impacted. Early-career women were more likely to fear retribution. Five themes emerged, including Flexible Expectations, Support, Mental Health, Compensation, and Communication. Pre-pandemic stress and burnout were rampant, and this study demonstrates that academic medicine faculty are still suffering. It is the authors' hope that administrations can utilize these data to make informed decisions regarding policies enacted to assist populations who are most vulnerable to the effects of the pandemic.