Joseph Sakel, Brittany Gass, Courtney Moore, B. Cockrum, Bridget Hawryluk, Lisa Parks, Kara Garcia, Tammy Sajdyk
Background and Hypothesis:The current 5-year survival rate for adolescent and young adult (AYA) cancer diagnoses is 85.8%. However, AYA cancer survivors face many challenges including loss of insurance, infertility, sexual health concerns, physical disability, education barriers, housing instability, food insecurity, and decreased financial well-being. Survivors in rural areas may face additional challenges, such as lack of access to cancer centers, tailored resources, and networks of fellow AYA cancer survivors that may be available in large cities. The study goal was to better understand specific barriers to survivorship care for this rural population, using a comprehensive interactive workbook distributed to cancer survivors in Southwest Indiana. Methods:A prototype workbook was distributed to 42 AYA survivors in southwest Indiana. Follow-up interviews were conducted with 11 individuals. Interviews with the first wave of eligible participants (n=7) provided perspectives on the workbook, helped identify potential improvements, and offered further insight into their survivorship experiences. These eligible participants were also invited to participate in an online forum to facilitate group discussions on potential improvements to the workbook. Responses were evaluated through affinity mapping to identify common themes. Results:AYA cancer was found to have a lasting impact on physical health, mental health, and relationships for many of the AYA survivors. Importantly, only 27% of participants who completed the workbook responded “yes” to having received a survivorship care plan, suggesting barriers in communication between survivors and healthcare providers. Regarding overall health, the three largest barriers identified by cancer survivors in rural southwest Indiana were insurance coverage, mental health services, and the availability of services needed. Conclusion:To strengthen survivorship care to rural survivors, our study suggests a need for better distribution and explanation of survivorship care plans, as well as increased access to stable insurance, medical services, and mental health services.
{"title":"Understanding Barriers Faced by Rural Adolescent and Young Adult Cancer Survivors","authors":"Joseph Sakel, Brittany Gass, Courtney Moore, B. Cockrum, Bridget Hawryluk, Lisa Parks, Kara Garcia, Tammy Sajdyk","doi":"10.18060/27766","DOIUrl":"https://doi.org/10.18060/27766","url":null,"abstract":"Background and Hypothesis:The current 5-year survival rate for adolescent and young adult (AYA) cancer diagnoses is 85.8%. However, AYA cancer survivors face many challenges including loss of insurance, infertility, sexual health concerns, physical disability, education barriers, housing instability, food insecurity, and decreased financial well-being. Survivors in rural areas may face additional challenges, such as lack of access to cancer centers, tailored resources, and networks of fellow AYA cancer survivors that may be available in large cities. The study goal was to better understand specific barriers to survivorship care for this rural population, using a comprehensive interactive workbook distributed to cancer survivors in Southwest Indiana. \u0000Methods:A prototype workbook was distributed to 42 AYA survivors in southwest Indiana. Follow-up interviews were conducted with 11 individuals. Interviews with the first wave of eligible participants (n=7) provided perspectives on the workbook, helped identify potential improvements, and offered further insight into their survivorship experiences. These eligible participants were also invited to participate in an online forum to facilitate group discussions on potential improvements to the workbook. Responses were evaluated through affinity mapping to identify common themes. \u0000Results:AYA cancer was found to have a lasting impact on physical health, mental health, and relationships for many of the AYA survivors. Importantly, only 27% of participants who completed the workbook responded “yes” to having received a survivorship care plan, suggesting barriers in communication between survivors and healthcare providers. Regarding overall health, the three largest barriers identified by cancer survivors in rural southwest Indiana were insurance coverage, mental health services, and the availability of services needed. \u0000Conclusion:To strengthen survivorship care to rural survivors, our study suggests a need for better distribution and explanation of survivorship care plans, as well as increased access to stable insurance, medical services, and mental health services.","PeriodicalId":20522,"journal":{"name":"Proceedings of IMPRS","volume":" 8","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139625635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jalyn Warren, Season Kealyn Johnson, Samantha Ackley, Reham Afifi, Rashmi Shrinivasan, Randy R. Brutkiewicz
Background: Amyloid beta (Aβ)-induced synaptic dysfunction and inflammation are features of Alzheimer’s disease (AD). One contributor to inflammation is mucosal-associated invariant T (MAIT) cells, an innate T cell that recognizes antigens presented by the MR1 molecule. Previously, we found increased MR1 expression in microglia near plaques and the loss of MR1/MAIT cell axis slowed the progression of Aβ pathology. This study aimed to determine contributions of the MR1/MAIT cell axis to immunity and synaptic proteins in the 5XFAD AD model mouse. Methods: We crossed 5XFAD mice with MR1-deficient mice (which lack MR1 and MAIT cells). At 2-, 4-, 6-, and 8-months of age, hippocampal and cortical brain tissue from wild-type, MR1KO, 5XFAD, and 5XFAD/MR1KO mice were analyzed by Western blot. Protein levels were analyzed with antibodies against GFAP (astrocytes), complement C3, and postsynaptic density protein (PSD)95. Additionally, Novel Object Recognition, Open Field, and Barnes Maze behavioral tests were performed in the 5XFAD mice to measure memory deficits. Results: Region-specific results were obtained for the hippocampus and cortex. The expression levels of PSD95 and C3 were significantly upregulated in the hippocampus of 5XFAD/MR1KO compared to 5XFAD mice at 6-8 months of age; in the cortex, GFAP levels were also significantly increased in 5XFAD/MR1KO mice. Finally, compared to wildtype C57BL/6 mice, 5XFAD mice showed memory deficits. Conclusions and Potential Impact: Approximately 6.7 million Americans are living with AD. This number is expected to double by 2050. Without any currently demonstrated therapy against AD, there is a need for therapeutic target(s) as part of novel treatment paradigms. Our results demonstrate an impact of the MR1/MAIT cell axis on postsynaptic proteins and consequent AD pathology. Thus, understanding the contribution of this axis could help reveal the role of innate immunity in AD and potentially serve as a future therapeutic target in AD patients.
{"title":"MR1/MAIT Cell Axis Impacts Innate Immunity and Synaptic Proteins in 5XFAD Mice","authors":"Jalyn Warren, Season Kealyn Johnson, Samantha Ackley, Reham Afifi, Rashmi Shrinivasan, Randy R. Brutkiewicz","doi":"10.18060/27827","DOIUrl":"https://doi.org/10.18060/27827","url":null,"abstract":"Background: \u0000Amyloid beta (Aβ)-induced synaptic dysfunction and inflammation are features of Alzheimer’s disease (AD). One contributor to inflammation is mucosal-associated invariant T (MAIT) cells, an innate T cell that recognizes antigens presented by the MR1 molecule. Previously, we found increased MR1 expression in microglia near plaques and the loss of MR1/MAIT cell axis slowed the progression of Aβ pathology. This study aimed to determine contributions of the MR1/MAIT cell axis to immunity and synaptic proteins in the 5XFAD AD model mouse. \u0000Methods: \u0000We crossed 5XFAD mice with MR1-deficient mice (which lack MR1 and MAIT cells). At 2-, 4-, 6-, and 8-months of age, hippocampal and cortical brain tissue from wild-type, MR1KO, 5XFAD, and 5XFAD/MR1KO mice were analyzed by Western blot. Protein levels were analyzed with antibodies against GFAP (astrocytes), complement C3, and postsynaptic density protein (PSD)95. Additionally, Novel Object Recognition, Open Field, and Barnes Maze behavioral tests were performed in the 5XFAD mice to measure memory deficits. \u0000Results: \u0000Region-specific results were obtained for the hippocampus and cortex. The expression levels of PSD95 and C3 were significantly upregulated in the hippocampus of 5XFAD/MR1KO compared to 5XFAD mice at 6-8 months of age; in the cortex, GFAP levels were also significantly increased in 5XFAD/MR1KO mice. Finally, compared to wildtype C57BL/6 mice, 5XFAD mice showed memory deficits. \u0000Conclusions and Potential Impact: \u0000Approximately 6.7 million Americans are living with AD. This number is expected to double by 2050. Without any currently demonstrated therapy against AD, there is a need for therapeutic target(s) as part of novel treatment paradigms. Our results demonstrate an impact of the MR1/MAIT cell axis on postsynaptic proteins and consequent AD pathology. Thus, understanding the contribution of this axis could help reveal the role of innate immunity in AD and potentially serve as a future therapeutic target in AD patients.","PeriodicalId":20522,"journal":{"name":"Proceedings of IMPRS","volume":" 11","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139625720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tejas Kandharkar, Matthew Ward, Anita Gupta, Thomas Nowak, THOMAS H. EVERETT IV
Background:Gastric Electrical Stimulation (GES) is a therapy for gastroparesis patients, alleviating symptoms like nausea, vomiting, and poor gastric emptying. The therapeutic impact of GES is believed to stem from changes in autonomic nerve activity, particularly parasympathetic activity via the vagal nerves. This study examines skin sympathetic nerve activity (SKNA) to assess autonomic nerve bursts, investigating the effects of GES on nerve activity and cardiac function. Methods:SKNA signals were recorded from 48 patients at three locations: left side of the neck (SKNA1), right side of the neck (SKNA2), and via ECG Lead 1 across the chest (SKNA3). Signals were band pass filtered (500 Hz to 1000 Hz) to eliminate ECG and muscle artifacts and highlight nerve activity. Using Labchart software, the absolute value integral (iSKNA) was calculated for each 100-millisecond sample, with resulting values exported to Excel. Data was collected during different GES conditions: GES On, GES at ½ voltage, GES Off, and GES back on. The threshold for nerve activity bursts was determined as the mean of iSKNA values + two times the standard deviation in each section. Results:Histograms of average aSKNA values showed reduced nerve activity with GES off. Left and vagal nerve activity on SKNA1 was significantly lower with GES fully on or off compared to GES at ½ voltage. No other significant differences were observed in variabilities or average aSKNAs in SKNA1 or SKNA2. Future Directions & Potential Impact:Burst analysis of iSKNA data will address key questions. Variations in burst activity with different GES conditions may elucidate GES's therapeutic effects on gastroparesis. Subsequent segmentation of data into patients with resolved and unresolved symptoms could reveal the relationship between burst activity and therapeutic efficacy. Additionally, correlation of burst data with heart rate variability analysis will provide insights into the impact of GES on cardiac function. This study will advance our understanding of GES effects and safety, potentially improving patient outcomes.
{"title":"Assessing Skin Sympathetic Nerve Activity and Cardiac Effects in Patients with Gastric Electrical Stimulation","authors":"Tejas Kandharkar, Matthew Ward, Anita Gupta, Thomas Nowak, THOMAS H. EVERETT IV","doi":"10.18060/27905","DOIUrl":"https://doi.org/10.18060/27905","url":null,"abstract":"Background:Gastric Electrical Stimulation (GES) is a therapy for gastroparesis patients, alleviating symptoms like nausea, vomiting, and poor gastric emptying. The therapeutic impact of GES is believed to stem from changes in autonomic nerve activity, particularly parasympathetic activity via the vagal nerves. This study examines skin sympathetic nerve activity (SKNA) to assess autonomic nerve bursts, investigating the effects of GES on nerve activity and cardiac function. \u0000Methods:SKNA signals were recorded from 48 patients at three locations: left side of the neck (SKNA1), right side of the neck (SKNA2), and via ECG Lead 1 across the chest (SKNA3). Signals were band pass filtered (500 Hz to 1000 Hz) to eliminate ECG and muscle artifacts and highlight nerve activity. Using Labchart software, the absolute value integral (iSKNA) was calculated for each 100-millisecond sample, with resulting values exported to Excel. Data was collected during different GES conditions: GES On, GES at ½ voltage, GES Off, and GES back on. The threshold for nerve activity bursts was determined as the mean of iSKNA values + two times the standard deviation in each section. \u0000Results:Histograms of average aSKNA values showed reduced nerve activity with GES off. Left and vagal nerve activity on SKNA1 was significantly lower with GES fully on or off compared to GES at ½ voltage. No other significant differences were observed in variabilities or average aSKNAs in SKNA1 or SKNA2. \u0000Future Directions & Potential Impact:Burst analysis of iSKNA data will address key questions. Variations in burst activity with different GES conditions may elucidate GES's therapeutic effects on gastroparesis. Subsequent segmentation of data into patients with resolved and unresolved symptoms could reveal the relationship between burst activity and therapeutic efficacy. Additionally, correlation of burst data with heart rate variability analysis will provide insights into the impact of GES on cardiac function. This study will advance our understanding of GES effects and safety, potentially improving patient outcomes.","PeriodicalId":20522,"journal":{"name":"Proceedings of IMPRS","volume":" 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139625730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hannah S. Wang, Elizabeth Scott, Murad K. Nazzal, Will Varner, Reginald S Parker, Tyler J. Margetts, Alexander Harris, Ashlyn Morris, Sonali J. Karnik, Rachel J. Blosser, Amy Creecy, Sarah L. Mostardo, Marko Dragisic, Jill C. Fehrenbacher, Kathryn D. Fischer, Alexandru Movila, Adrian L. Oblak, Melissa A. Kacena
Alzheimer’s disease and related dementias (AD/ADRD) are multifactorial, highly heterogeneous, and complex age-dependent disorders that severely affect memory and cognitive function, impacting nearly 35.6 million people worldwide. In the elderly, dementia increases the risk of falls and fractures by 2-3 times, due in part to neurovascular instability, low bone mineral density due to pre-existing osteoporosis, and poor musculature supporting joints due to cachexia and/or sarcopenia. While the occurrence of fractures due to AD/ADRD is well documented, an association between fractures and AD/ADRD onset or progression is underappreciated and warrants additional investigation. We aim to investigate the mechanistic actions underlying fracture healing as a precipitating event for AD/ADRD pathogenesis. Four-month-old, male, 5xFAD (AD model) and wild-type control (C57BL/6) mice were divided into 2 groups: surgically induced femoral fractures and uninjured mice. Prior to surgery mice underwent baseline AD behavior testing including: spontaneous alternation in the y-maze, light-dark exploration in the open field, and active place avoidance assays. Mice are undergoing weekly x-ray imaging to monitor fracture healing progression and longitudinal AD behavior testing. 22 weeks post-surgery mice will be euthanized, and femurs and brains collected. Femurs will undergo uCT imaging and histological assessment of bone healing and immunohistochemical assessment of inflammatory markers. Brains will be processed for histology and neuroinflammatory marker analysis, including Aβ plaque deposition, tau tangles, neuronal survival, neurogenesis, and activation/proliferation of microglia and astrocytes. At the conclusion of the study, we expect to see an increase in neuroinflammatory markers and delayed fracture healing in the experimental 5xFAD group. We anticipate that compared to uninjured controls, femoral fracture results in cognitive decline, Aβaccumulation/neurodegeneration, increases in neuroinflammation, and vascular impairment. We anticipate finding a correlation between fracture and worsened AD outcomes. By uncovering the mechanisms underlying this relationship, we hope to guide future studies to develop more robust therapeutics.
{"title":"Fracture-Induced Effects on the Onset & Progression of Alzheimer’s Disease","authors":"Hannah S. Wang, Elizabeth Scott, Murad K. Nazzal, Will Varner, Reginald S Parker, Tyler J. Margetts, Alexander Harris, Ashlyn Morris, Sonali J. Karnik, Rachel J. Blosser, Amy Creecy, Sarah L. Mostardo, Marko Dragisic, Jill C. Fehrenbacher, Kathryn D. Fischer, Alexandru Movila, Adrian L. Oblak, Melissa A. Kacena","doi":"10.18060/27875","DOIUrl":"https://doi.org/10.18060/27875","url":null,"abstract":"Alzheimer’s disease and related dementias (AD/ADRD) are multifactorial, highly heterogeneous, and complex age-dependent disorders that severely affect memory and cognitive function, impacting nearly 35.6 million people worldwide. In the elderly, dementia increases the risk of falls and fractures by 2-3 times, due in part to neurovascular instability, low bone mineral density due to pre-existing osteoporosis, and poor musculature supporting joints due to cachexia and/or sarcopenia. \u0000While the occurrence of fractures due to AD/ADRD is well documented, an association between fractures and AD/ADRD onset or progression is underappreciated and warrants additional investigation. We aim to investigate the mechanistic actions underlying fracture healing as a precipitating event for AD/ADRD pathogenesis. \u0000Four-month-old, male, 5xFAD (AD model) and wild-type control (C57BL/6) mice were divided into 2 groups: surgically induced femoral fractures and uninjured mice. Prior to surgery mice underwent baseline AD behavior testing including: spontaneous alternation in the y-maze, light-dark exploration in the open field, and active place avoidance assays. Mice are undergoing weekly x-ray imaging to monitor fracture healing progression and longitudinal AD behavior testing. 22 weeks post-surgery mice will be euthanized, and femurs and brains collected. Femurs will undergo uCT imaging and histological assessment of bone healing and immunohistochemical assessment of inflammatory markers. Brains will be processed for histology and neuroinflammatory marker analysis, including Aβ plaque deposition, tau tangles, neuronal survival, neurogenesis, and activation/proliferation of microglia and astrocytes. \u0000At the conclusion of the study, we expect to see an increase in neuroinflammatory markers and delayed fracture healing in the experimental 5xFAD group. We anticipate that compared to uninjured controls, femoral fracture results in cognitive decline, Aβaccumulation/neurodegeneration, increases in neuroinflammation, and vascular impairment. We anticipate finding a correlation between fracture and worsened AD outcomes. By uncovering the mechanisms underlying this relationship, we hope to guide future studies to develop more robust therapeutics.","PeriodicalId":20522,"journal":{"name":"Proceedings of IMPRS","volume":" 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139625819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: In medical school, where learning an abundance of information in a short period of time is required, it is necessary that learners receive valuable feedback after summative assessments (i.e., unit exams). First-year medical students at Indiana University School of Medicine (IUSM) begin their education with a course titled Human Structure (HS), followed by Molecules to Cells and Tissues (MCT). Both courses provided different formats for exam feedback, resulting in anecdotal comments about preference and utility of feedback. This study uses qualitative research methods to examine IUSM-Bloomington students’ perceptions of exam feedback formats with respect to their utility and applicability. Methods: Five, second-year IUSM-Bloomington medical students participated in a focus group to discuss their utilization and perceived usefulness of HS and MCT exam feedback. A thematic analysis was used to interpret data from the focus group. This study was deemed exempt by the IU-IRB (19409). Results: The thematic analysis revealed that students’ discussions fell into three categories: logistics, utilization, and mentality. These categories were further broken into themes and subthemes, revealing 13 unique codes. Students spent a substantial amount of time discussing logistics of exam feedback. Barriers to utilization of exam feedback included a lack of information provided at the feedback sessions and a lack of time in the schedule available for feedback sessions. Students preferred MCT approach to exam feedback, however they recognized HS course logistics may prevent similar adoption. Students had small suggestions on how to improve feedback in both courses. Conclusions/Implications: The data suggest students would benefit from small changes in how first-year medical school courses at IUSM provide exam feedback. Improvements could include extending the time of exam review sessions, incorporating a discussion on commonly missed exam concepts, providing answer explanations for incorrect and correct answers, and transitioning statewide reviews to be campus led.
{"title":"Student Perceptions of Two Preclinical Medical School Exam Feedback Approaches","authors":"Elsie Gasaway, Valerie O’Loughlin","doi":"10.18060/27851","DOIUrl":"https://doi.org/10.18060/27851","url":null,"abstract":"Background: In medical school, where learning an abundance of information in a short period of time is required, it is necessary that learners receive valuable feedback after summative assessments (i.e., unit exams). First-year medical students at Indiana University School of Medicine (IUSM) begin their education with a course titled Human Structure (HS), followed by Molecules to Cells and Tissues (MCT). Both courses provided different formats for exam feedback, resulting in anecdotal comments about preference and utility of feedback. This study uses qualitative research methods to examine IUSM-Bloomington students’ perceptions of exam feedback formats with respect to their utility and applicability. \u0000Methods: Five, second-year IUSM-Bloomington medical students participated in a focus group to discuss their utilization and perceived usefulness of HS and MCT exam feedback. A thematic analysis was used to interpret data from the focus group. This study was deemed exempt by the IU-IRB (19409). \u0000Results: The thematic analysis revealed that students’ discussions fell into three categories: logistics, utilization, and mentality. These categories were further broken into themes and subthemes, revealing 13 unique codes. Students spent a substantial amount of time discussing logistics of exam feedback. Barriers to utilization of exam feedback included a lack of information provided at the feedback sessions and a lack of time in the schedule available for feedback sessions. Students preferred MCT approach to exam feedback, however they recognized HS course logistics may prevent similar adoption. Students had small suggestions on how to improve feedback in both courses. \u0000Conclusions/Implications: The data suggest students would benefit from small changes in how first-year medical school courses at IUSM provide exam feedback. Improvements could include extending the time of exam review sessions, incorporating a discussion on commonly missed exam concepts, providing answer explanations for incorrect and correct answers, and transitioning statewide reviews to be campus led.","PeriodicalId":20522,"journal":{"name":"Proceedings of IMPRS","volume":" 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139625829","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mackenzie Schaff, Andrew Kim, Evan Arsenault, Mary Musselman, Dushani Ranasinghe, Margaret Schwarz
Background/Objective: Chronic lung disease of prematurity, bronchopulmonary dysplasia (BPD) occurs when infants born with underdeveloped immature lungs are forced to navigate the expansion of future air spaces, with irregular vascular formation proceeding development of BPD. Lung development has distinct and dynamic metabolic requirements. We recently identified by mass spectrometry that nicotinamide adenine dinucleotide (NAD+), generated from vitamin B3 ‘Nicotinamide’ (NAM), was significantly reduced in a hyperoxia murine model of BPD. As NAM/NAD+ are dynamic regulators of tissue regenerating neovascularization in otherdisease processes, we hypothesized that NAM/NAD+ metabolic deficiencies contribute to compromised angiogenesis formation and alveolar formation. Methods: Impact of NAM supplementation on circulating human neonatal endothelial colonyforming cells (ECFCs) were assessed for differential capillary formation properties of angiogenesis (Matrigel), migration (wound healing), proliferation (WST1 and crystal violetstaining), and mitochondrial function in normoxia and hyperoxia (85% oxygen) conditions. Results: Hyperoxia suppresses ECFC angiogenesis, while NAM supplementation in hyperoxia significantly rescued vascular networks, branched nodes, and branch points (p<0.001). Wound healing assays suggest that NAM promotes cell migration in normoxia and hyperoxia (p<0.0001). Although NAM increased WST1 activity in hyperoxia, crystal violet analysis determined that NAM had no impact on ECFC proliferation. Lastly, NAM significantly reduced hyperoxia induced mitochondrial oxidative stress in a dose dependent manner (p<0.05). Conclusion and Clinical Implications: Lung development has specific metabolic needs during different stages of development that are disrupted by premature birth. Replenishment of NAM promotes angiogenesis and migration in hyperoxia while reducing mitochondrial activity. Future studies are necessary to explore the role of NAM/NAD+ axis in the developing lung.
背景/目的：早产儿慢性肺部疾病--支气管肺发育不良（BPD）是指出生时肺部发育不成熟的婴儿被迫引导未来气腔的扩张，不规则的血管形成导致 BPD 的发生。肺的发育有独特的动态代谢要求。我们最近通过质谱分析发现，在高氧鼠 BPD 模型中，由维生素 B3 "烟酰胺"（NAM）生成的烟酰胺腺嘌呤二核苷酸（NAD+）显著减少。由于 NAM/NAD+ 是其他疾病过程中组织再生新生血管的动态调节因子，我们推测 NAM/NAD+ 代谢缺乏会导致血管生成和肺泡形成受损。方法：补充 NAM在正常氧和高氧（85% 氧）条件下，评估补充 NAM 对循环中的人类新生儿内皮集落形成细胞（ECFCs）在血管生成（Matrigel）、迁移（伤口愈合）、增殖（WST1 和结晶紫染色）和线粒体功能方面不同毛细血管形成特性的影响。结果高氧抑制了 ECFC 的血管生成，而在高氧条件下补充 NAM 能显著修复血管网络、分支节点和分支点（p<0.001）。伤口愈合试验表明，在常氧和超氧状态下，NAM能促进细胞迁移（p<0.0001）。虽然 NAM 增加了高氧条件下的 WST1 活性，但水晶紫分析表明，NAM 对 ECFC 的增殖没有影响。最后，NAM 以剂量依赖的方式大大降低了高氧诱导的线粒体氧化应激（p<0.05）。结论和临床意义：肺部发育在不同阶段有特定的代谢需求，而早产会破坏这些需求。补充 NAM 可促进高氧状态下的血管生成和迁移，同时降低线粒体活性。未来的研究有必要探索 NAM/NAD+ 轴在肺发育中的作用。
{"title":"Energizing the Lung Vasculature in the Premature Infant to Promote Alveolar Formation","authors":"Mackenzie Schaff, Andrew Kim, Evan Arsenault, Mary Musselman, Dushani Ranasinghe, Margaret Schwarz","doi":"10.18060/27774","DOIUrl":"https://doi.org/10.18060/27774","url":null,"abstract":"Background/Objective: Chronic lung disease of prematurity, bronchopulmonary dysplasia (BPD) occurs when infants born with underdeveloped immature lungs are forced to navigate the expansion of future air spaces, with irregular vascular formation proceeding development of BPD. Lung development has distinct and dynamic metabolic requirements. We recently identified by mass spectrometry that nicotinamide adenine dinucleotide (NAD+), generated from vitamin B3 ‘Nicotinamide’ (NAM), was significantly reduced in a hyperoxia murine model of BPD. As NAM/NAD+ are dynamic regulators of tissue regenerating neovascularization in otherdisease processes, we hypothesized that NAM/NAD+ metabolic deficiencies contribute to compromised angiogenesis formation and alveolar formation. \u0000Methods: Impact of NAM supplementation on circulating human neonatal endothelial colonyforming cells (ECFCs) were assessed for differential capillary formation properties of angiogenesis (Matrigel), migration (wound healing), proliferation (WST1 and crystal violetstaining), and mitochondrial function in normoxia and hyperoxia (85% oxygen) conditions. \u0000Results: Hyperoxia suppresses ECFC angiogenesis, while NAM supplementation in hyperoxia significantly rescued vascular networks, branched nodes, and branch points (p<0.001). Wound healing assays suggest that NAM promotes cell migration in normoxia and hyperoxia (p<0.0001). Although NAM increased WST1 activity in hyperoxia, crystal violet analysis determined that NAM had no impact on ECFC proliferation. Lastly, NAM significantly reduced hyperoxia induced mitochondrial oxidative stress in a dose dependent manner (p<0.05). \u0000Conclusion and Clinical Implications: Lung development has specific metabolic needs during different stages of development that are disrupted by premature birth. Replenishment of NAM promotes angiogenesis and migration in hyperoxia while reducing mitochondrial activity. Future studies are necessary to explore the role of NAM/NAD+ axis in the developing lung.","PeriodicalId":20522,"journal":{"name":"Proceedings of IMPRS","volume":" 13","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139626184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Introduction: Celiac disease is a common autoimmune illness precipitated by the ingestion of gluten, a protein contained in grains (e.g., wheat, barley, and rye). Celiac disease can present with a wide variety of manifestations across nearly any body system, but most individuals with celiac disease present with subclinical symptoms. Despite relatively inexpensive testing and an effective treatment (i.e., a gluten free diet), most individuals with celiac disease remain undiagnosed, leading to significant disease burden. Research suggests that physicians have poor knowledge of celiac disease, likely contributing to the high rates of missed diagnoses. This study sought to assess the information encountered by students in pre-clinical medical education regarding celiac disease. Methods: Information was drawn from recent literature to create a rubric to evaluate the presentation of celiac disease in curricular and educational resources for pre-clinical medical students. Categories evaluated included prevalence, morbidity/mortality, manifestations, comorbidities, and testing recommendations. This rubric was used to assess the curriculum from a large US medical school and First Aid for the USMLE Step 1, a popular commercial resource used by medical students. Results: The medical school curriculum scored higher overall than First Aid (31/48 and 12/48, respectively). The curriculum also scored higher in all categories except morbidity/mortality. The curriculum showed deficits predominantly in morbidity/mortality and testing recommendations. First Aid showed deficits in all categories. Discussion: Results showed that the medical school curriculum provided more complete information about several aspects of celiac disease. First Aid did not thoroughly address any of the categories evaluated with the rubric. While First Aid may be an effective consolidation of Step 1 material, it seems likely that it is focused on “teaching to the test” rather than providing thorough medical education for future physicians. The medical curriculum is a more complete resource for students to learn about celiac disease.
{"title":"Celiac Disease in Medical Curriculum","authors":"Elizabeth Kerns, Polly R. Husmann, PhD","doi":"10.18060/27966","DOIUrl":"https://doi.org/10.18060/27966","url":null,"abstract":"Introduction: Celiac disease is a common autoimmune illness precipitated by the ingestion of gluten, a protein contained in grains (e.g., wheat, barley, and rye). Celiac disease can present with a wide variety of manifestations across nearly any body system, but most individuals with celiac disease present with subclinical symptoms. Despite relatively inexpensive testing and an effective treatment (i.e., a gluten free diet), most individuals with celiac disease remain undiagnosed, leading to significant disease burden. Research suggests that physicians have poor knowledge of celiac disease, likely contributing to the high rates of missed diagnoses. This study sought to assess the information encountered by students in pre-clinical medical education regarding celiac disease. \u0000Methods: Information was drawn from recent literature to create a rubric to evaluate the presentation of celiac disease in curricular and educational resources for pre-clinical medical students. Categories evaluated included prevalence, morbidity/mortality, manifestations, comorbidities, and testing recommendations. This rubric was used to assess the curriculum from a large US medical school and First Aid for the USMLE Step 1, a popular commercial resource used by medical students. \u0000Results: The medical school curriculum scored higher overall than First Aid (31/48 and 12/48, respectively). The curriculum also scored higher in all categories except morbidity/mortality. The curriculum showed deficits predominantly in morbidity/mortality and testing recommendations. First Aid showed deficits in all categories. \u0000Discussion: Results showed that the medical school curriculum provided more complete information about several aspects of celiac disease. First Aid did not thoroughly address any of the categories evaluated with the rubric. While First Aid may be an effective consolidation of Step 1 material, it seems likely that it is focused on “teaching to the test” rather than providing thorough medical education for future physicians. The medical curriculum is a more complete resource for students to learn about celiac disease.","PeriodicalId":20522,"journal":{"name":"Proceedings of IMPRS","volume":" 26","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139627209","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jacquelyn Knobelsdorf, Sandra K. Althouse, Sandeep Batra
Background: Adolescent and young adult (AYA, 15-39 years old) patients with acute lymphoblastic leukemia (ALL) often experience pancytopenia and severe immunosuppression. Particularly during intensive phases of chemotherapy, allogeneic blood transfusion support is essential in their care. The utilization of both red blood cell (RBC) and platelet transfusions, as well as the thresholds used to determine when transfusions are needed, are poorly described in this population. The objective of this study is to describe blood product utilization in AYA patients with ALL treated at our institution. Methods: A cohort of 20 AYA patients with ALL treated at Riley Hospital for Children from October 2020 to July 2023 were identified for data collection. Pre- and post-transfusion laboratory values, transfusion totals, comorbid events or complications, transfusion reactions, and minimal residual disease (MRD) values were collected and analyzed. All values reported are mean ± standard deviation for continuous variables and n (%) for categorical variables. Values were calculated individually for each patient for each phase of therapy and averaged across all patients. Results: Patients studied had varying needs for transfusions throughout their therapy (50.75 ± 48.06), with an average of 22.95 ± 15.65 RBC transfusions and 25.60 ± 29.65 platelet transfusions. Patients being treated with standard chemotherapy protocols required moretransfusions during induction (14.13 ± 21.56) and delayed intensification (14.07 ± 24.29) phases compared to other phases. Patients with MRD positive status required more transfusions (69.14 ± 58.14) than patients with MRD negative status (40.92 ± 40.84). Conclusions and Potential Impacts: This study helped to elucidate the need for transfusions among the AYA ALL patient population, throughout the different phases of treatment. These findings hold implications for establishing guidelines that could clarify when transfusions should be given in this population, helping physicians provide the best care to future patients.
背景：患有急性淋巴细胞白血病（ALL）的青少年和年轻成人（AYA，15-39 岁）患者通常会出现泛泛性贫血和严重的免疫抑制。特别是在强化化疗阶段，异体输血支持对他们的治疗至关重要。目前对这一人群输注红细胞（RBC）和血小板的使用情况以及确定何时需要输血的阈值还缺乏描述。本研究旨在描述在本院接受治疗的青壮年 ALL 患者的血液制品使用情况。方法：我们确定了 20 名于 2020 年 10 月至 2023 年 7 月在莱利儿童医院接受治疗的 AYA ALL 患者，并收集了他们的数据。收集并分析了输血前和输血后的实验室值、输血总量、合并症或并发症、输血反应和最小残留病（MRD）值。对于连续变量，报告的所有数值均为平均值 ± 标准差；对于分类变量，报告的数值均为 n (%)。每个患者在每个治疗阶段的数值单独计算，所有患者的数值取平均值。结果所研究的患者在整个治疗过程中的输血需求各不相同（50.75 ± 48.06），平均输注红细胞（22.95 ± 15.65）次，血小板（25.60 ± 29.65）次。与其他阶段相比，接受标准化疗方案治疗的患者在诱导阶段（14.13 ± 21.56）和延迟强化阶段（14.07 ± 24.29）需要更多的输血。MRD 阳性患者需要的输血量（69.14 ± 58.14）高于 MRD 阴性患者（40.92 ± 40.84）。结论和潜在影响：这项研究有助于阐明青少年 ALL 患者在不同治疗阶段的输血需求。这些发现对制定指导原则具有重要意义，指导原则可明确该人群何时需要输血，从而帮助医生为未来的患者提供最佳治疗。
{"title":"Blood Product Utilization Among Adolescent and Young Adult Patients with Acute Lymphoblastic Leukemia: A Single Center Ex","authors":"Jacquelyn Knobelsdorf, Sandra K. Althouse, Sandeep Batra","doi":"10.18060/27865","DOIUrl":"https://doi.org/10.18060/27865","url":null,"abstract":"Background: Adolescent and young adult (AYA, 15-39 years old) patients with acute lymphoblastic leukemia (ALL) often experience pancytopenia and severe immunosuppression. Particularly during intensive phases of chemotherapy, allogeneic blood transfusion support is essential in their care. The utilization of both red blood cell (RBC) and platelet transfusions, as well as the thresholds used to determine when transfusions are needed, are poorly described in this population. The objective of this study is to describe blood product utilization in AYA patients with ALL treated at our institution. \u0000Methods: A cohort of 20 AYA patients with ALL treated at Riley Hospital for Children from October 2020 to July 2023 were identified for data collection. Pre- and post-transfusion laboratory values, transfusion totals, comorbid events or complications, transfusion reactions, and minimal residual disease (MRD) values were collected and analyzed. All values reported are mean ± standard deviation for continuous variables and n (%) for categorical variables. Values were calculated individually for each patient for each phase of therapy and averaged across all patients. \u0000Results: Patients studied had varying needs for transfusions throughout their therapy (50.75 ± 48.06), with an average of 22.95 ± 15.65 RBC transfusions and 25.60 ± 29.65 platelet transfusions. Patients being treated with standard chemotherapy protocols required moretransfusions during induction (14.13 ± 21.56) and delayed intensification (14.07 ± 24.29) phases compared to other phases. Patients with MRD positive status required more transfusions (69.14 ± 58.14) than patients with MRD negative status (40.92 ± 40.84). \u0000Conclusions and Potential Impacts: This study helped to elucidate the need for transfusions among the AYA ALL patient population, throughout the different phases of treatment. These findings hold implications for establishing guidelines that could clarify when transfusions should be given in this population, helping physicians provide the best care to future patients.","PeriodicalId":20522,"journal":{"name":"Proceedings of IMPRS","volume":"8 51","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139437767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background/Objective: Blood cultures are vital for diagnosing infections and directing antibiotic therapy to causative organisms in systemically ill patients. Blood culture contamination contributes to increased costs, longer lengths of stay, and unnecessary antibiotic use. Certain patient histories and demographics have been associated with higher contamination rates. Identifying contamination risk factors within the hospital may allow for improvements in patient care. Methods: Patient demographics, history, and blood culture information were identified through a chart review for all adult blood cultures collected in January 2023 at the IU Health Bloomington Hospital. Patient characteristics collected included age, race, ethnicity, BMI, and a number of comorbidities (COPD, diabetes, etc.). Blood culture characteristics, including the number of cultures drawn, hospital setting, etc., were also collected. A comparative analysis was performed between positive, negative, and contaminated cultures. Results: In January, 443 adult patients had blood cultures collected at IUH Bloomington hospital, with contamination in 33 cases (7.4%). Patients with contaminated cultures had a higher prevalence of hypertension (75.8%) compared to those with negative cultures (61.9%). Type II diabetes was more prominent in the contaminated culture group (36.4%) than the negative culture group (31.3%). 15.2% of patients with contaminated cultures resided in extended care facilities, while only 12.3% of patients with negative cultures did so. Most contaminated cultures (97%) were drawn in the emergency department, with 3% collected in medical-surgical units/floor level of care. Conclusion: Features of patient history, demographics, and culture collection may be associated with higher blood culture contamination rates. Scientific/Clinical/Policy Impact and Implications: This data will be expanded into the entire 1st quarter of 2023 to further identify trends in culture contamination. Findings may present opportunities for quality improvement in patient care as IUH Bloomington looks to further reduce their rates of contaminated cultures.
背景/目的：血液培养对于诊断感染和针对全身性疾病患者的致病菌进行抗生素治疗至关重要。血培养污染会导致成本增加、住院时间延长和不必要的抗生素使用。某些患者病史和人口统计学特征与较高的污染率有关。识别医院内的污染风险因素可改善患者护理。方法：通过对 2023 年 1 月在 IU Health Bloomington 医院收集的所有成人血培养物进行病历审查，确定了患者的人口统计学特征、病史和血培养信息。收集的患者特征包括年龄、种族、民族、体重指数和一些合并症（慢性阻塞性肺病、糖尿病等）。此外，还收集了血培养特征，包括抽血培养次数、医院环境等。对阳性培养物、阴性培养物和污染培养物进行了比较分析。结果今年 1 月，布鲁明顿国际大学医院共为 443 名成年患者采集了血培养物，其中 33 例（7.4%）受到污染。与阴性培养物患者（61.9%）相比，培养物污染患者的高血压发病率更高（75.8%）。与阴性培养物组（31.3%）相比，受污染培养物组（36.4%）的 II 型糖尿病发病率更高。15.2%的培养物污染患者居住在长期护理机构，而只有 12.3%的培养物阴性患者居住在长期护理机构。大多数受污染的培养物（97%）是在急诊科提取的，3%是在内外科病房/楼层护理中提取的。结论患者病史、人口统计学特征和培养物采集可能与较高的血液培养污染率有关。科学/临床/政策影响和意义：该数据将扩展到整个 2023 年第一季度，以进一步确定培养污染的趋势。随着布卢明顿国际大学医院希望进一步降低培养物污染率，研究结果可能会为改善患者护理质量提供机会。
{"title":"Blood Culture Contamination Rates in Bloomington, Association with Patient History","authors":"Vanessa Schwieterman, Aimee Lee, Christine Motzkus","doi":"10.18060/27781","DOIUrl":"https://doi.org/10.18060/27781","url":null,"abstract":"Background/Objective: Blood cultures are vital for diagnosing infections and directing antibiotic therapy to causative organisms in systemically ill patients. Blood culture contamination contributes to increased costs, longer lengths of stay, and unnecessary antibiotic use. Certain patient histories and demographics have been associated with higher contamination rates. Identifying contamination risk factors within the hospital may allow for improvements in patient care. \u0000Methods: Patient demographics, history, and blood culture information were identified through a chart review for all adult blood cultures collected in January 2023 at the IU Health Bloomington Hospital. Patient characteristics collected included age, race, ethnicity, BMI, and a number of comorbidities (COPD, diabetes, etc.). Blood culture characteristics, including the number of cultures drawn, hospital setting, etc., were also collected. A comparative analysis was performed between positive, negative, and contaminated cultures. \u0000Results: In January, 443 adult patients had blood cultures collected at IUH Bloomington hospital, with contamination in 33 cases (7.4%). Patients with contaminated cultures had a higher prevalence of hypertension (75.8%) compared to those with negative cultures (61.9%). Type II diabetes was more prominent in the contaminated culture group (36.4%) than the negative culture group (31.3%). 15.2% of patients with contaminated cultures resided in extended care facilities, while only 12.3% of patients with negative cultures did so. Most contaminated cultures (97%) were drawn in the emergency department, with 3% collected in medical-surgical units/floor level of care. \u0000Conclusion: Features of patient history, demographics, and culture collection may be associated with higher blood culture contamination rates. \u0000Scientific/Clinical/Policy Impact and Implications: This data will be expanded into the entire 1st quarter of 2023 to further identify trends in culture contamination. Findings may present opportunities for quality improvement in patient care as IUH Bloomington looks to further reduce their rates of contaminated cultures.","PeriodicalId":20522,"journal":{"name":"Proceedings of IMPRS","volume":"4 9","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139438057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Salil J. Gupta, Shahna Shahul Hameed, Tasneem Sharma
Purpose: Glaucoma is a group of optic neuropathies characterized by visual field loss, classically due to increased intraocular pressure (IOP) and retinal ganglion cell (RGC) degeneration. Current treatment options reduce IOP, but RGC degeneration persists. De novoRGCs can be differentiated from reprogrammed human corneal fibroblasts and transplanted into the retina to potentially restore vision in patients with late-stage disease when most RGCs are irreversibly damaged. We investigate the survival of these human induced pluripotent stem cell (IPSC) derived RGCs after culturing them in human donor eyes under conditions of elevated and normal IOP using the ocular translaminar autonomous system (TAS) chamber. Methods: Human iPSCs were generated by reprogramming human donor corneal fibroblasts using Sendai viral vectors with Yamanaka factors. These iPSCs were then differentiated into retinal organoids from which RGCs were obtained. The RGCs were transduced with AAV2-GFP and transplanted into donor human eyes obtained from control individuals. They were pressurized for approximately 5 days, with the left eye maintained at normal IOP and right eye at elevated IOP. Viability was measured by expression levels of pro-survival pathways via qRTPCR, immunohistochemistry staining, and electroretinography for retinal function (ERG). Results: We successfully transplanted human RGCs into human donor eyes and visualized them after GFP transduction. We maintained a pressure differential between the two eyes for approximately 5 days using the TAS model. Differential expression of survival, inflammatory and apoptotic genes was identified between normal and high IOP. We identified retinal function changes under normal and high IOP after RGC transplantation. Conclusions: Human iPSC derived RGCs provide a potential strategy to overcome vision loss in patients with diseases that damage RGCs such as glaucoma, Parkinson’s, Alzheimer's, multiple sclerosis, and traumatic optic neuropathy. Future investigation would involve integration of transplanted RGCs and directing their axons towards visual centers in the brain.
{"title":"Viability of Transplanted De Novo Retinal Ganglion Cells in Human Donor Eyes Maintained Under Elevated Intraocular Pressure","authors":"Salil J. Gupta, Shahna Shahul Hameed, Tasneem Sharma","doi":"10.18060/27900","DOIUrl":"https://doi.org/10.18060/27900","url":null,"abstract":"Purpose: Glaucoma is a group of optic neuropathies characterized by visual field loss, classically due to increased intraocular pressure (IOP) and retinal ganglion cell (RGC) degeneration. Current treatment options reduce IOP, but RGC degeneration persists. De novoRGCs can be differentiated from reprogrammed human corneal fibroblasts and transplanted into the retina to potentially restore vision in patients with late-stage disease when most RGCs are irreversibly damaged. We investigate the survival of these human induced pluripotent stem cell (IPSC) derived RGCs after culturing them in human donor eyes under conditions of elevated and normal IOP using the ocular translaminar autonomous system (TAS) chamber. \u0000Methods: Human iPSCs were generated by reprogramming human donor corneal fibroblasts using Sendai viral vectors with Yamanaka factors. These iPSCs were then differentiated into retinal organoids from which RGCs were obtained. The RGCs were transduced with AAV2-GFP and transplanted into donor human eyes obtained from control individuals. They were pressurized for approximately 5 days, with the left eye maintained at normal IOP and right eye at elevated IOP. Viability was measured by expression levels of pro-survival pathways via qRTPCR, immunohistochemistry staining, and electroretinography for retinal function (ERG). \u0000Results: We successfully transplanted human RGCs into human donor eyes and visualized them after GFP transduction. We maintained a pressure differential between the two eyes for approximately 5 days using the TAS model. Differential expression of survival, inflammatory and apoptotic genes was identified between normal and high IOP. We identified retinal function changes under normal and high IOP after RGC transplantation. \u0000Conclusions: Human iPSC derived RGCs provide a potential strategy to overcome vision loss in patients with diseases that damage RGCs such as glaucoma, Parkinson’s, Alzheimer's, multiple sclerosis, and traumatic optic neuropathy. Future investigation would involve integration of transplanted RGCs and directing their axons towards visual centers in the brain.","PeriodicalId":20522,"journal":{"name":"Proceedings of IMPRS","volume":"2 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139438142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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