bluuebunny/crossref_metadata_2025 huggingface dataset:
Antibody blockade of CD47‐SIRPα axis is protective in the murine model of Experimental Autoimmune Encephalomyelitis
Authors: Velazquez Francisco E , Autio Anu , Newton Gail , Luscinskas Francis William
Published: June 2021

CD47 and its interaction with Signal Regulatory Protein alpha (SIRPα) play an important role in immune cell homeostasis. Our lab has previously demonstrated that CD47 on both endothelium and T cells plays an important role in T cell adhesion and diapedesis in vivo and in vitro, and that CD47−/− CD4+ T cells have impaired antigen‐mediated proliferation in the mouse model of Experimental Autoimmune Encephalomyelitis (EAE). Given the reports that CD47−/− mice and mice expressing a nonsignaling mutant SIRPα transgene are protected from developing EAE, suggests CD47 is a therapeutic target. However, a previous study found anti‐CD47 monoclonal antibody (mAb) MIAP301 treatment at the same time as myelin oligodendrocyte glycoprotein (MOG) immunization of mice delayed onset of disease and that treatment at peak of disease in animals resulted in a more severe disease. This “Janus like” effect has not been studied further. Using in vitro flow adhesion assays, here we show that mAb MIAP301 blocks both in cis (with LFA‐1 integrin) and in trans (with SIRPα) interactions of CD47 and that a different mAb MIAP410, blocks the SIRPα interaction and not LFA‐1‐ICAM‐1 interaction. We hypothesized that targeting only the “in trans” SIRPα interaction with MIAP410 in EAE would be protective. Thus we treated MOG immunized mice with MIAP410 or an isotype control IgG1 and investigated the leukocyte infiltration into the spinal cord using mass cytometry. Strikingly, treatment with MIAP410 prevented a more severe form of EAE when given at disease peak and was protective when given simultaneously with MOG. Mechanistically, MIAP410 had a profound inhibitory effect (68% inhibition) on the infiltration of IL‐23+ IFN‐γ producing γδ T cells into the spinal cord of the CNS with no significant differences observed on other immune cell infiltration such as Th17 cells. Additionally, we observed that there was decreased neutrophil and conventional dendritic cell infiltration in the spinal cord of MIAP410 as compared to IgG treated mice. Based on these findings, we conclude that CD47‐SIRPα interactions are necessary for the infiltration of pathogenic γδ T cells that express IL‐23R and promote leukocyte infiltration and neuronal damage in EAE.

Support or Funding Information

T32 HL007627R01 HL125780R

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Novel Junctional Adhesion Molecule‐Like (JAML) Regulates Neutrophil Transepithelial Migration During Intestinal Inflammation
Authors: Azcutia Veronica , Kelm Matthias , Hilgarth Roland , Nusrat Asma , Parkos Charles A.
Published: June 2021

Neutrophil (PMN) migration in the intestine is an essential component of host defense and wound repair. However, dysregulated PMN recruitment is a hallmark of inflammatory bowel disease (IBD). Disease flares in IBD are associated with robust PMN migrating across the intestinal mucosa resulting in crypt abscess formation and mucosal ulceration. Despite strong association of PMN infiltration into the gut with patient symptoms in IBD, the molecular basis of PMN transepithelial migration (TEpM) represents a significantly understudied area. It is now appreciated that PMN migration into intestinal mucosa requires multiple adhesive interactions between migrating PMN and intestinal epithelial cells (IECs), that represents a multi‐step process facilitated by complex interactions between PMN and IEC expressed proteins including members of the Junctional Adhesion Molecules (JAMs) family. We have reported that the novel JAM‐like protein termed JAML expressed on PMN, associates with the coxsackie and adenovirus receptor (CAR) expressed on epithelial cells. Binding of soluble JAML ectodomains to CAR has been shown to disrupt JAML‐CAR interactions and reduce PMN TEpM in‐vitro. To define the molecular mechanism of JAML regulation of PMN TEpM during intestinal inflammation in‐vivo, we generated JAML knockout mice (JAML−/−). PMN TEpM was evaluated using a small intestinal loop model, and PMN migration in response to the chemoattractant LTB4 (1nM) quantified by flow cytometry. While WT and JAML−/− mice had similar numbers of circulating leukocytes, we observed reduced PMN TEpM in‐vivo in JAML−/− mice compared to WT animals. This decrease in PMN traffic into the lumen was associated with increased retention of PMN within the intestinal epithelium in JAML−/− mice. In addition, epithelial accumulation of PMN in JAML−/− mice paralleled an increase in intestinal permeability to a 4KDa FITC‐dextran as detected by fluorescence intensity in serum. Finally, we studied the role of JAML on susceptibility to DSS induced colitis. Loss of JAML markedly increased disease activity index, inflammation and mucosal ulceration compared to WT mice. Overall, these observations suggest that JAML is an important adhesion molecule that regulates PMN TEpM in the intestinal mucosa. JAML thus represents a new therapeutic target to dampen excessive PMN migration during intestinal inflammation as seen in IBD.

Support or Funding Information

CCFA CDA454814 and NIH 3R01 DK072564‐23S1

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
“This Is How You Do It, Right?!” Practical Suggestions for Designing and Implementing Education Research Projects within the Anatomy Classroom
Authors: Bentley Danielle Christine , Rosner Tamara , Hum Gregory , McCloy Cora
Published: June 2021

Anatomy educators have become leaders in the Scholarship of Teaching and Learning (SoTL) within the biomedical sciences. Our classrooms and laboratories are learning hubs filled with innovative, evidence‐based pedagogies that we commonly systematically evaluate for learning effectiveness. As we continue to push the boundaries of innovative teaching, we must be careful to ensure we are developing, implementing, and disseminating education research projects with strong and resilient designs. Within the broad field of SoTL and education research there are common design flaws that can be avoided with careful preparation and forethought. Specifically, this presentation will focus on six themes of education research each with common concerns: 1) selecting an appropriate methodology and data collection strategy that best aligns with the specific research question(s), 2) establishing appropriate and informative comparison groups, 3) using randomization to control for between‐student factors (and to avoid self‐selection bias), 4) including appropriate considerations of power differential when using one's own students as research participants, 5) obtaining informed consent in a manner that respects student autonomy, and 6) selecting robust statistical analyses that fit the research design. Each theme will be thoroughly expanded upon in the context of the anatomy classroom/laboratory with concrete, practical suggestions for effective and meaningful SoTL projects. Positive examples will be extracted from recently published works to showcase exemplary research designs in the field. Ultimately, the goal of this presentation is to initiate and fuel constructive conversations on education research design elements; a conversation that will benefit junior and senior anatomy educators alike. By encouraging and facilitating strong, resilient, and thoughtful education research projects, anatomy educators can continue to be at the forefront of innovative SoTL practices that enhance learning for our students and positively impact biomedical education at large.

Support or Funding Information

n/a

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Creating Educator Scholar Leaders—Curriculum Development of a New PhD Program in Anatomy Education
Authors: Terrell Mark , Kulesza Randy
Published: June 2021

INTRODUCTION

Anatomy education is perhaps experiencing the best and the worst of times. It may be the best of times because so much hard work has been done by many anatomists over the past three decades to develop more effective and evidence‐based educational practices and technological tools to maximize student learning. The worst of times may be near as forces transform medical curricula and create a paucity of new anatomists as faculty retire and new schools are created/expanded.

AIM

Using the arguments from both contexts, we sought to create a unique PhD program in Anatomy Education.

METHODS

Applying Kern's six step approach to curriculum development in medical education, we successfully merged the strengths and existing resources of two educational programs at LECOM to create a new PhD program in Anatomy Education.

RESULTS

Three critical components of this curricular endeavor include the educational preparation in transforming teaching and learning practices in anatomy; tight coherence and integration among anatomical and pedagogical knowledge, skills, and behaviors through clinical and educational supervision; and developing strategies for meeting challenges facing program approval at the institutional and accreditation levels. Several PhD students have marticulated and positively favor the new program.

CONCLUSION

This program has a strong commitment to producing a unique breed of new anatomists as education specialists who have the knowledge, skills and behaviors needed to lead health professions education development and research, thereby enhancing academic programs, improving health care outcomes, and strengthening the anatomical profession.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Comparison of Students' Performance in Multiple‐Choice vs. Short Answer Question Formats in Anatomy Spotter Exams
Authors: Bataineh Ziad Mohydeen
Published: June 2021

Introduction

Anatomy spotter exam in the Anatomy Department at Sultan Qaboos University comprised identification of macroscopic and microscopic structures and questions related to their blood supply, innervation, normal and abnormal X‐rays, MRI and CT scan images, and embryological origins and abnormalities. We used the multiple choice format (MCF) and the short answer format (SAF) to assess the medical students. The students' performance in different courses across the test type were not assessed

Aim

In this study, medical students' performance in two formats of anatomy spotter exams were compared; the multiple choice format (MCF) and the short answer format (SAF).

Results

Results of spotter exams from three courses were used in this study, the cardiovascular system (CVS) and the respiratory system (RS), third year students, and the head and neck (H&N) fourth year students. For each system, a comparison of students' performance in SAF vs. MCF was made. The main factors in this comparison were the question type and the subject material of the course assessed.

Our results indicate that in all courses assessed students' performance in MCF was either similar or slightly better than in the SAF. Students performed best in the CVS course and worst in the RS course regardless of the spotter type used. In addition, the MCF required less time to carryout.

Discussion and Conclusion

On the other hand, student's performance in the SAF may have partially depended more on his ability to recall factual knowledge such as anatomical terminologies, structures' names and their correct spelling. We conclude that the spotter exams with the MCF are at least as effective as the SAF and may equally depend on Student's problem solving skills, and his ability to synthesize, communicate knowledge and make rational decisions.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Assessing Self‐assessment in Anatomy
Authors: Kingston Amanda K. , Garofalo Evan M. , Cardoza Kristinmae , Fisher Rebecca E.
Published: June 2021

Introduction

Formative self‐assessments are frequently utilized in anatomy courses to gauge learning. Self‐assessment tools have been demonstrated to improve student learning and performance on exams. However, few studies have assessed how specific elements, such as the inclusion of visual components, Bloom's taxonomy level, and the degree of topic integration, influence the efficacy of self‐assessments in an anatomy course.

Aim

This study retrospectively examined the relationships between self‐assessment construction characteristics, exam construction characteristics, and student exam performance. Specifically, 1) What elements of exam question construction correlated with performance? and 2) What elements of self‐assessment questions correlated with performance on corresponding exam questions?

Methods

Self‐assessment and exam questions administered during the Clinical Anatomy Block at the University of Arizona College of Medicine ‐ Phoenix from 2014–2018 for the Thorax and Abdomen and Pelvis and Lower Extremity units were examined. Self‐assessment questions were distributed to students via email, while exams took place in the anatomy laboratory, with a majority of questions incorporating structures on the donors, images, or anatomical models. For all questions, the constituent learning objectives, use of visual components, Bloom's taxonomy level, and degree of topic integration were noted. Exam performance data were collected for each class as the percentage correct for each question. These variables were entered into linear multiple regression models to assess their relationship to student performance for individual learning objectives. Because no individually identifiable data were utilized in this study, IRB approval was waived by the University of Arizona Office of Research, Discovery & Innovation (Protocol #: 1810045386).

Results

Regression analysis indicates that having visual components in exam questions is negatively associated with performance (t = −5.53, p <0.00). Conversely, a higher average Bloom's level for targeted learning objectives in self‐assessments (t = 2.02, p = 0.04), and a greater number of image‐based questions (t = 2.33, p = 0.02) are positively correlated with performance on corresponding exam questions.

Conclusions

These findings provide evidence that elements of self‐assessment construction, such as a visual component and a higher cognitive level, influence student exam performance when the exam format also incorporates these elements.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Does Familiarization with Virtual Reality Improve Anatomy Learning in a Virtual Reality Environment?
Authors: Gill Jaskaran , Aggarwal Akanksha , Birk Sapriya , Hass Katrina , Mitchell Josh , Fenesi Barbara , Wainman Bruce
Published: June 2021

Despite a scarcity in substantive evidence, virtual reality (VR) is heralded as the future of anatomy education. Recent research in our lab suggests that VR headsets are substantially inferior to traditional plastic models as educational tools. This effect appears to be mediated by the VR headsets' inability to create convincing stereopsis. Our study aims to investigate if familiarization with the VR environment improves performance. When presented with a new learning environment (e.g., a room in VR), one may encounter a “novelty effect” where the new environment demands focus and distracts from learning. An introduction to the VR environment prior to learning could minimize this effect. Therefore, we hypothesize that familiarization will improve test scores. Undergraduate university students with no prior formal anatomy education (n=50) will be randomized to a familiarization or non‐familiarization group. The former group is allowed to orient themselves with a VR car engine model, ad libitum. Then, both groups will undergo a learning phase with a VR pelvis model for 10 minutes. Participants will be tested using a 15‐item evaluation, consisting of an equal amount of nominal, spatial, and functional questions, immediately and 48 hours after learning. Preliminary data (n=8) suggest that there are currently no statistically significant differences in short‐ or long‐term evaluation scores (p=0.109, p=0.254, respectively) between the familiarization and non‐familizarization groups. If this trend persists through completion of the study, it would suggest that a familiarization phase does not improve test scores. Data collection and analysis are anticipated to be completed in January 2019. Gaining an understanding of which factors influence VR learning allows it to become a more effective, evidence‐based tool for anatomy education.

Support or Funding Information

Self‐funded.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The Effect of Virtual Three‐Dimensional Stereoscopic Middle and Inner Ear Models on First‐Year Dental Students' Short‐Term Retention
Authors: Meyer Edgar R. , Warren Susan , Thompson Kenneth , Cui Dongmei
Published: June 2021

Several studies in virtual three‐dimensional (3D) anatomy have shown either no difference in traditional and 3D learning among dental students or disadvantages in 3D learning over traditional learning. There are few studies in the literature that explore the effectiveness of virtual stereoscopic 3D anatomy models on dental students' learning. This study aimed to determine if virtual 3D stereoscopic anatomical models of the middle and inner ear could improve first‐year dental students' short‐term retention. This study also aimed to determine if there was a correlation between first‐year dental students' spatial abilities and their learning gains from virtual 3D anatomy exposure. During the fall 2018 semester, the first‐year dental students were invited to participate in 3D learning sessions pertaining to the middle and inner ear. Students (n=18) attended to a 3D learning session featuring virtual stereoscopic middle and inner ear models. During the learning session, the student participants completed a pre‐test before and a post‐test after the virtual 3D learning experience. At the end of the 3D learning sessions, students completed a mental rotation test (MRT) for measuring their spatial abilities and a survey for assessing their perceptions of 3D learning. The average scores on all of the students' performance measures, pre‐tests, post‐tests, and MRT's, will be analyzed using a repeated measures ANOVA. In addition, the pre‐ and post‐ knowledge test performances, respectively, of the students with high and low spatial ability will be compared using a one‐way ANOVA. The results of the statistical analyses will determine whether there is a significant difference between the pre‐ and post‐3D test scores of the first‐year dental students and whether there is a significant relationship between first‐year dental students' spatial abilities and learning. Overall, the first‐year dental students perceived the 3D learning sessions of middle and inner ear anatomy to be a positive learning experience. The use of virtual stereoscopic 3D anatomy has the potential to improve first‐year dental students' learning of the anatomy of regions as complex as the middle and inner ear when used as a supplement to traditional instruction.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
3D Anatomy Application (App): A Supplemental Learning Aid for Upper Extremity Anatomy Occupational Therapy Courses
Authors: Rosario Martin G , Hyder Aneesah , Gonzalez‐Sola Maryvi
Published: June 2021

Traditionally, graduate anatomy is learned from books, cadaver dissections, and prosections. During a lecture, the most common tool for presentations are screen projections such as PowerPoint presentations. Although this method has its teaching/learning advantage, it remains a 2‐dimensional surface unfavorable for depth perception, anatomical relationships, and clinical applications. Currently, there are several tools for the enhancement of learning and teaching anatomy, such as 3D virtual anatomy apps and anatomical models.

Purpose

Enhance learning through anatomy 3D applications integrated into an Upper Extremity Anatomy course for occupational therapy (OT) students.

Methods

There were 46 OT students (2 males and 44 females) enrolled in the TWU Summer 2018 Upper extremity anatomy course from the Dallas and Houston campuses. In supporting the lecture component, 3‐dimensional animations (“Complete Anatomy” app on an iPad Pro) of different anatomical upper extremity structures were projected to the big screen for the students to improve their understanding of the anatomy content that was covered. Upon course completion, the students were requested to provide their feedback and impressions regarding this combined teaching technique. Questions were tailored to examine the students' perception of integrating the app into the course, preference of the different tools used in the course, as well as their opinion on using this tool in the future.

Results

96% of the students reported that the anatomy app was very helpful (85%–39/46), helpful (9%–4/46) or good (2%–1/46) in aiding to their comprehension of complex anatomy structures. It was found that the anatomy app was preferred secondly to the hands‐on prosection as a teaching tool. Moreover, 100% of the students considered that the anatomy app would be a helpful tool in OT Upper Extremity courses.

Conclusion

Combining the 3D anatomy apps into graduate anatomy courses appears to be a useful tool for the comprehensive learning of human anatomy. This is demonstrated by the selection of the 3D app by graduate students as the second best teaching tool to learn anatomy.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Visualizing Prenatal Twin Anatomy: A Parent Education Resource for Twin‐Twin Transfusion Syndrome
Authors: Castillo Christine Joy , Lee Lisa MJ , Behrendt Nicholas , Marwan Ahmed
Published: June 2021

Twin‐twin transfusion syndrome (TTTS) is a complication occurring in 10–20% of monochorionic diamniotic multiple pregnancies characterized by unequal circulation due to placental anastomoses. Left untreated, chronic TTTS has an 80–100% mortality rate, with sequelae including cardiovascular, neurodevelopmental and renal anomalies in surviving infants. Prognosis is improved by timely diagnosis and intervention, with selective fetoscopic laser photocoagulation emerging as the front‐line treatment. Considering poor prognosis and the urgent need for invasive treatment, TTTS announcement is a traumatic event for expectant parents regardless of survival outcome, thus adequate support from their providers is essential. Parent perception of their care relies on receiving ample information, and while antenatal multidisciplinary consultations at fetal centers provide space for parent education, parents often have difficulty understanding the fetal and placental anatomy. Currently, at the Colorado Fetal Care Center, supplemental educational resources include 2D images and literature intended for a scientific audience. The objective of this project was to develop and implement an interactive 3D virtual model of TTTS during antenatal consultations to facilitate parent education. The model was developed from deidentified fetal MRI Digital Imaging and Communications in Medicine (DICOM) data demonstrating TTTS (COMIRB # 18‐1955). A total of 10 MRI datasets (6 with selective intrauterine growth restriction (SIUGR), 4 without SIUGR) were identified as possible candidates. One dataset was selected for model construction based on representation of the pathology. The DICOM data was segmented on 3D Slicer. The segmentations were imported into Blender for 3D rendering and to smooth artifacts, then published onto Sketchfab for user interaction. The tool was assessed by obstetric and surgical specialists for accuracy. By providing an anatomically accurate fetal, placental, and pathologic anastomosis visualization, this model can assist providers in demonstrating the diagnosis, explaining prognosis, and discussing potential treatment options. The new 3D, interactive virtual TTTS model has the potential to improve parents' experience by increasing patient knowledge and engaging them in the intervention planning required to optimize fetal outcomes. Further investigation is required to determine the efficacy and educational value of the model.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Neuron Enteric Death Is Mediated by S100B During Intestinal Mucositis Induced by 5‐Fluorouracil
Authors: da Silva Costa Daniely Viana , da Silva Costa Deiziane Viana , Bon‐Frauches Ana Carina , Silva Angeline Maria Holanda Pascoal , Moura‐Neto Lauro Inacio , Martins Conceição Silva , Moura‐Neto Vivaldo Carina , de Castro Brito Gerly Anne
Published: June 2021

The goal of this study was to investigate whether S100B is involved in 5‐FU‐induced enteric neuron death during intestinal mucositis. This study was approved by ethical committee of Federal university of Ceará (protocol n° 80/2015). Intestinal mucositis was induced by injecting a single dose of 5‐FU (450 mg/kg, IP) and the mice were euthanized after 3 days. The mice were pretreated with Pentamidine, an S100B inhibitor, (4 mg/kg daily) for three days. The animals were euthanized and small intestine tissues (duodenum, jejunum and ileum) were collected to evaluate S100B expression by Western Blot, enteric neuron alterations by immunohistochemistry for HuC/D (neuron marker), neuronal death by TUNEL Assay and double staining of HuC/D with RAGE or NFκB NLS. A primary culture of enteric neuron from the small intestine was performed to evaluate the direct effect of 5‐FU and S100B in neuron death using a TUNEL assay. 5‐FU reduced (p<0.01) HuC/D protein expression and increased (p<0.01) S100B protein expression in the small intestine, as well as increased (p<0.01) TUNEL positive cells on jejunum of mice compared with control group. 5‐FU enhanced RAGE and NFκB NLS immunostaining in enteric neurons in the jejunum compared to control group. Pentamidine prevented (p<0.01) these alterations induced by 5‐FU in the intestine. Higher S100B concentration, but not 5‐FU, directly caused (p<0.0001) enteric neuron death. This study showed an important role for enteric glia cells in 5‐FU‐induced enteric neuron death via S100B, during intestinal mucositis. Our results suggest that enteric glial cells release S100B, which in turn activates NFκB signaling through RAGE activation in neurons, leading to neuronal cell death during intestinal mucositis induced by 5‐FU. Therefore, the S100B signaling pathway appears to be a promising pharmacological target to prevent 5‐FU‐induced enteric neuron death.

Support or Funding Information

PROCAD/CAPES, CNPq, FUNCAP

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Impact of Deep Brain Stimulation of the Subthalamic Nucleus on Neuropsychological Outcomes and Voxel‐Based‐Morphometric‐Analyses in Parkinson's Disease Patients
Authors: Clemens Athena , Thompson John A.
Published: June 2021

Parkinson's Disease (PD) is a movement disorder that is characterized by tremor, rigidity, and bradykinesia, due to significant cell‐death of the dopaminergic neurons in the substantia nigra. Deep brain stimulation (DBS) is a surgical intervention used to treat PD patients in which stimulating electrodes are placed bilaterally, most often in the subthalamic nucleus (STN). STN‐DBS is restricted to those who respond sufficiently well to a dopaminergic medication regimen. This procedure alleviates the motor symptoms associated with PD. Historically, the majority of clinical research on STN‐DBS has focused on motor outcomes. Until recently, few studies had explored the effect of STN‐DBS on post‐surgical cognitive and memory outcomes. Moreover, the relationship between cognitive outcomes and neuroanatomical changes in PD patients with STN‐DBS is largely unknown. The goal of this study was to correlate pre‐ and post‐ surgical memory and cognitive neuropsychological outcomes with volumetric changes in relevant neuroanatomical structures before and after DBS intervention. Thus far, 11 PD patients met inclusion criteria for this Colorado Multiple Institutional Review Board (COMIRB) approved study (COMIRB 16‐1060). Voxel‐based‐morphometry of cortical and subcortical brain regions were used to assess structural changes in T1‐weighted MR. Analyzed neuropsychological measures include those from the second edition of the California Verbal Language Test (CVLT‐II). Preliminary neuropsychological analyses suggest that Standard CVLT‐II Long Delayed Free recall of List Learning decreases post surgically. Further neuropsychological and neuroanatomical analyses are ongoing. This study is relevant because it will better characterize neuroanatomical and neurofunctional changes that occur with STN‐DBS so that physicians are better prepared to support their patients after STN‐DBS. Eventually, studies like this one may lead to predictive measures which allow physicians to better screen for patients who will benefit most from DBS surgery based on neuropsychological pre‐testing.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Repeated mild traumatic brain injury in the juvenile brain: Investigations on synaptic plasticity in the hippocampus
Authors: Pinar Cristina , Fontaine Christine J , Christie Brian , Nahirney Patrick C
Published: June 2021

Traumatic Brain Injury (TBI) occurs when an impulsive force is transmitted to the head and affects the brain. Up to 75% of all brain injuries are classified as “mild” TBI (mTBI; also known as concussion). There is growing evidence that during a life time repeated mTBI (rmTBI) can produce cumulative structural damage and long‐term changes in behaviour. The juvenile brain is in a period of robust synaptic reorganization and myelination, making this a particularly vulnerable time to incur either mTBI or rmTBI. Although most children recover from mTBI incidents, a significant proportion experience learning and memory impairments after rmTBI. Memory formation is closely dependent on the capacity of the brain to regulate long‐lasting changes in neuronal communication (synaptic plasticity) with the hippocampus being an essential structure for this process. Therefore, we hypothesize that rmTBI causes learning and memory deficits through its effects on hippocampal synaptic plasticity.

Using the Awake Closed‐Head Injury (ACHI) model we examined how male and female Long‐Evans rats (25–28 days of age) responded after 8 episodes of ACHI over a four day period in. Animals were assessed for changes in their state of consciousness and sensorimotor abilities immediately following each ACHI, allowing us to examine the acute effects of each injury. Synaptic plasticity was assessed using in vitro electrophysiology either one day or seven days post‐ACHI.

Our results show that rmTBI impacts sensorimotor abilities and impairs hippocampal synaptic plasticity in both males and female subjects. These data suggest that learning and memory deficits from rmTBI may be due to impairments in hippocampal synaptic plasticity.

Support or Funding Information

Support or Funding Information Canadian Institutes of Health Research (CIHR) Natural Sciences and Engineering Research Council of Canada (NSERC) CP funded by Fundació Universitaria Agustí Pedro Pons

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Following unilateral spinal contusion pregabalin has an at‐time effect on pruritus and a protective effect on mechanosensory nociception, but does not improve ipsilateral motor outcomes with early administration in rats
Authors: Erskine Erin , Tetzlaff Wolfram , Plunet Ward , Salterio Nicholas , Smaila Brittney , Kramer John , Ramer Matthew
Published: June 2021

Anticonvulsants like pregabalin (PGB) are the first‐line treatment for neuropathic pain caused by traumatic injury and non‐traumatic diseases of the central nervous system. Recent evidence from a human cohort study suggests that early use of pregabalin after spinal cord injury (SCI) may result in improved motor scores, however, it is unknown to what extent changes in spinal neural circuitry are involved. Using a rat model of unilateral cervical contusion, we examined the effect of pregabalin treatment on both motor and sensory function. For four weeks post‐injury, rats were given daily pregabalin or filtered water via oral gavage. Motor function was scored using the Montoya staircase assessment for food pellet retrieval (MSA). Additionally, pruritus and noxious mechosensation were assessed through behavioural evidence of scratching and the Randall‐Selitto analgesiometre, respectively. Finally, we used immunohistochemistry to characterize the primary afferent axons responsible for conveying signals related to nociception and itch. We found no significant relationship between the early administration of pregabalin and improved motor scores in the affected forelimb following MSA analysis. However, rats receiving pregabalin had improved performance on the MSA using their contralateral paw, suggesting alleviation of ongoing pain. Additionally, we found that self‐injurious scratching, often displayed by animals with this type of injury, was greatly reduced in those treated with PGB. However, following a two‐month sham injury experiment without PGB treatment, it was found that the scratching was not necessarily due to SCI, except for a small number of cases in which scratching included the territory of the greater auricular nerve. Furthermore, results of the Randall‐Selitto analgesiometre indicate a protective effect that lasted after discontinuation of PGB. Finally, we saw no changes in the density of pruritic and nociceptive primary afferents just rostral to the site of injury. Our findings suggest that in rats with a unilateral SCI, PGB treatment has a possible protective effect on mechanosensory nociception, aids in diminishing pain and itch during use, and contrary to the human cohort study, does not improve motor outcomes with early administration.

Support or Funding Information

Wings for Life; Natural Sciences and Engineering Research Council (NSERC)

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Propithecus diadema Infant Survival is not Influenced by Yearly Rainfall or Mother's Dental Wear
Authors: Heffernan Katie SusAnn , Samonds Karen , Irwin Mitchell
Published: June 2021

Primate teeth wear through time in response to their environment. This change in topography has potential to affect nutrients absorbed, reproductive success, and fitness. King et al. suggested that for Propithecus edwardsi older females with dental senescence are unable to process certain types of foods, leading to higher infant mortality rate during weaning in years with insufficient rain. This study tested this hypothesis in Propithecus diadema from Tsinjoarivo, Madagascar living in fragmented landscapes, and exhibiting changes in diet and group dynamics compared to those living in pristine forests. These rapid changes could have detrimental consequences on reproductive success, and could be further influenced by environmental fluctuations like rainfall.

Infant deaths were compared to yearly rainfall totals and the mother's dental relief index, slope, and angularity. Compared to the King et al. study, rainfall totals averaged 1000 mm less at Tsinjoarivo, and dental wear was not as severe. At Tsinjoarivo, rainfall and dental wear did not appear to influence infant survival. This study indicates that the long‐term viability of Propithecus diadema at Tsinjoarivo is stable and positive. However, continued monitoring of this population is critical; while they may be able adapt to current habitat modifications, the continuation of forest destruction could still severely impact their viability.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Factors Impacting Bone Remineralization in Children with Through Knee Amputation
Authors: Coker Karen , Hubbert Douglas , Raynes Edilberto , Bowman Marsha
Published: June 2021

A relationship between bone density and prosthetic use exists among all individuals with lower limb amputations. The selection of suspension in prosthetic design and distal limb weight bearing affect the non‐density of the residual limb. The aim of the study was to identify the factors that impact positive bone remineralization in children with through knee amputation.

A systematic review of peer reviewed journals of physical therapy interventions, prosthetic socket and suspension design, and through knee amputations in children was done. Eighteen articles met the inclusion criteria. Bone mineral density loss after an amputation surgery is typical but the extent of loss can be minimized by the multifocal approach of physical therapy with gait training, properly fitting prosthetics with weight‐bearing designs.

Physical therapists are crucial to this approach with assessment and training in mobility and gait, especially in children with post amputation. The through knee amputation allows for increased weight bearing as well as the skin fit suspension and socket design. By weight bearing remineralization of lost bone in the residual limb is possible in the patient with through knee amputation.

Support or Funding Information

No funding sources were used.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Treatment with Exercise and Genistein Improves Fracture Resistance in Mice Fed High‐Fat, High‐Sugar Diet
Authors: Hellings Austin , Buchan Levi , Castro Monica , Al‐Nakkash Layla , Broderick Tom L , Plochocki Jeffrey H
Published: June 2021

Diets high in fat and sugar (HFSD) adversely affect bone mineralization during growth and are implicated in osteoporosis in obese adults. In this study, we assessed fracture risk in mice fed a standard diet and mice fed HFSD. We evaluated fracture risk using three‐point bending tests and comparisons of cross‐sectional geometric properties of the femur. We also investigated the effects of low‐intensity exercise and dietary genistein, an isoflavone, on fracture risk in HFSD‐fed mice. We tested the hypothesis using 50 male and 50 female C57BL/6 mice aged six weeks, which we divided into five treatment groups: lean control, HFSD control, HFSD + exercise, HFSD + genistein, and HFSD + exercise + genistein. Lean control mice were fed standard rodent chow. HFSD consisted of chow with 60% fat content and drinking water with 42 g/L sugar (55% sucrose, 45% fructose). Exercise training consisted of treadmill running for 30 min/day, 5 days/week. Genistein was given at a dose of 600 mg/kg diet. Comparisons of body mass and blood plasma revealed mice fed HFSD were obese and hyperglycemic by the end of the 12‐week treatment period. Statistical analysis of the data showed no differences in cross‐sectional geometric properties in comparisons of lean and HSFD‐fed mice (P > 0.05). However, mice fed HFSD and treated with exercise and genistein had significantly increased maximum second moments of area relative to HFSD controls (P < 0.05). Femurs of these mice also exhibited greater ultimate force during three‐point bending tests (i.e. maximum force recorded at the time of fracture) than HFSD controls (P < 0.05). Femurs of HFSD‐fed mice treated with exercise and genistein also demonstrated reduced corrected total bone fluorescence (CTBF) relative to HFSD controls (P < 0.05). CTBF quantifies advanced glycation end products (AGEs) in bone matrix. It is an indicator of fracture risk related to increased bone brittleness and reflects a reduced capacity to deform under loading. Our findings show treatment with low intensity exercise and dietary genistein increased fracture resistance in mice fed HFSD. These results suggest exercise and genistein benefit bone health in individuals with HFSD‐induced obesity.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Three‐dimensional visualization of cranial soft tissues in embryonic and early postnatal mice using phosphotungstic acid enhanced microCT
Authors: Lesciotto Kate M. , Motch Perrine Susan M. , Kawasaki Mizuho , Stecko Timothy , Ryan Timothy M. , Kawasaki Kazuhiko , Richstmeier Joan T.
Published: June 2021

Acquiring three‐dimensional imaging of animal specimens utilized in genetic, developmental, and evolutionary studies has typically been based on microCT (bone and mineralized tissues) and magnetic resonance microscopy (soft and un‐mineralized tissues). However, recent advances in microCT imaging have allowed for 1–5 μm resolution for small biological specimens, while typical microMRI imaging can generally only produce data with a resolution of approximately 30–40 μm. In order to achieve high‐resolution 3D visualization of soft tissues, the use of various contrast agents have been proposed, including iodine, osmium, and phosphotungstic acid (PTA). We investigated protocols for using PTA to stain soft tissues of the head in embryonic and early postnatal mice to enhance visualization of soft tissues by microCT imaging. Protocols for mice between embryonic day 13.5 and postnatal day 7 have been developed that allow for the visualization, segmentation, quantification, and analysis of soft tissue structures. Stained specimens were mounted in a 50:50 mix of polyester and paraffin waxes within a small tube and scanned on the GE v|tome|x L300 scanner in the Center for Quantitative Imaging at Pennsylvania State University with voxel dimensions between 1 and 10 μm, depending on specimen size. Multiple soft tissue structures, including the eye, inner ear, cartilage, muscle, glandular tissue, and brain, are easily differentiated in the resultant scans. Images of PTA‐stained specimens can be superimposed with microCT images of the same specimen before PTA staining to enable the study of relationships between hard and soft tissues in the same individual. This approach to both 2D and 3D visualization of soft tissues in murine models has immediate implications for understanding developmental processes and integration between hard and soft tissues of the cranium.

Support or Funding Information

National Science Foundation Grant BCS‐1731909, and NIDCR R01DE027677 and R01 DE022988

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The paediatric knee: A medical imaging assessment analysis
Authors: PATHER Nalini
Published: June 2021

Introduction

In recent years, there has been an increase in sport‐related injuries in the paediatric population. Improved imaging of musculoskeletal structures has also raised the need to better understand the changing morphology of the musculoskeletal structures during infant and child development. This study therefore aimed to investigate the morphology of bony elements of the paediatric knee at different ages from medical imaging data.

Methods

Erect knee CT (n=60) and MRI (n=72) DICOM images were obtained for 132 paediatric patients between 2–15 years (mean, 11.35 ±3.18) of age. The morphometry of nine parameters including notch width (NW), bicondylar width (BW), notch width index (NWI), tibial eminence height (TEH) and width (TEW), and femoral and tibial growth plate height (GPH) and width (GPW) were analysed and correlated with age and sex.

Results

In summary, the mean±SD for each parameter was: NW, 9.55 ±2.6; BW, 69.63 ±8.56; NWI, 0.14 ±0.03; TEH, 8.53 ±1.73; TEW, 27.52 ±4.12; FGPH, 1.25 ±0.71; and TGPH, 1.21 ±0.72. NW, BW, NWI, TEH and TEW had a significant positive linear correlation with age. NW, NWI and TEH had strong positive linear correlations with all variables except tibial slope, and femoral and tibial GPH. Femoral and tibial GPH correlated well with each other.

Conclusions

Applied anatomical knowledge of paediatric knee to clinical practice can possibly improve diagnosis and patient management, and assist in predicting injury patterns. Further longitudinal studies will assist in accurately mapping growth of each knee structure with age.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Investigating Undergraduate Student Misconceptions Regarding Pedigree Analysis
Authors: James Olena , Boury Nancy , Grimes Zachary , Reid Joshua , Wasendorf Chloe , Couch Brock , Seipelt‐Thiemann Rebecca
Published: June 2021

Genetics is a difficult topic for undergraduate biology students to comprehend because the topics are abstract, complex, use specific terminology, and require thinking across multiple scales, including the symbolic scale. Education regarding the most basic genetics concepts begins in mid‐elementary grades with distinct concepts repeated and built upon through high school. However, students also transfer information from popular culture and through making their own meaning of observed phenomena. Therefore, when students arrive to a genetics course, they have pre‐instructional knowledge about genetics topics some of which are misconceptions and/or naïve conceptions. The aim of this project was to investigate common misconceptions and naïve conceptions in undergraduate courses for pedigree analysis. Pedigree analysis is a common tool that involves thinking across the symbolic scale, distinct terminology, and the application of Mendelian and non‐Mendelian genetic principles. Open‐ended questions were used to gather student answers for three distinct learning objectives. Student answers were analyzed and grouped according to each student's conceptual errors. Terminology, the ability to gather the appropriate information from questions, and the symbolic nature of pedigree analysis were major problems for students and represent major, cross‐cutting problems with many genetics concepts. In addition, students' answers also revealed problems with understanding autosomal versus sex‐linked inheritance as well as confusion about the nature and relationship of genes and alleles. Furthermore, some students used reasoning associated with population level genetics, which shows a lack of understanding about mathematical probability and its relationship to inheritance for an individual. Future studies aim to utilize these data to investigate a schema theory approach to formation and organization of conceptual understanding for pedigree analysis.

Support or Funding Information

NSF Award : 1710262

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.