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Understanding Barriers Faced by Rural Adolescent and Young Adult Cancer Survivors 了解农村青少年和年轻成人癌症幸存者面临的障碍
Pub Date : 2024-01-11 DOI: 10.18060/27766
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.
背景与假设:目前,青少年癌症患者的 5 年存活率为 85.8%。然而,青少年和青年癌症幸存者面临着许多挑战,包括失去保险、不孕不育、性健康问题、身体残疾、教育障碍、住房不稳定、食品不安全和经济状况下降。农村地区的幸存者可能面临更多的挑战,如无法进入癌症中心、无法获得量身定制的资源、无法与大城市中的青壮年癌症幸存者建立联系。这项研究的目的是通过向印第安纳州西南部的癌症幸存者分发综合互动工作手册,更好地了解这一农村人口在幸存者护理方面面临的具体障碍。方法:向印第安纳州西南部的 42 名青壮年幸存者分发了工作手册原型。对 11 人进行了后续访谈。对第一批符合条件的参与者(7 人)进行了访谈,了解了他们对工作手册的看法,帮助确定了可能的改进措施,并进一步了解了他们的幸存者经历。这些符合条件的参与者还受邀参加了一个在线论坛,以便就工作手册可能的改进之处进行小组讨论。通过亲和图对回复进行评估,以确定共同的主题。结果:研究发现,青少年癌症对许多青少年幸存者的身体健康、心理健康和人际关系产生了持久的影响。重要的是,在完成工作手册的参与者中,只有 27% 回答 "是",表示已收到幸存者护理计划,这表明幸存者与医疗服务提供者之间的沟通存在障碍。在整体健康方面,印第安纳州西南部农村地区的癌症幸存者认为最大的三个障碍是保险范围、心理健康服务和所需服务的可用性。结论:为了加强对农村幸存者的幸存者关怀,我们的研究表明需要更好地分发和解释幸存者关怀计划,并增加获得稳定保险、医疗服务和心理健康服务的机会。
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引用次数: 0
MR1/MAIT Cell Axis Impacts Innate Immunity and Synaptic Proteins in 5XFAD Mice MR1/MAIT 细胞轴影响 5XFAD 小鼠的先天免疫和突触蛋白
Pub Date : 2024-01-11 DOI: 10.18060/27827
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.
背景:淀粉样β(Aβ)诱导的突触功能障碍和炎症是阿尔茨海默病(AD)的特征。导致炎症的一个因素是粘膜相关不变T(MAIT)细胞,这是一种先天性T细胞,能识别由MR1分子呈现的抗原。此前,我们发现斑块附近的小胶质细胞中 MR1 表达增加,MR1/MAIT 细胞轴的缺失减缓了 Aβ 病理学的进展。本研究旨在确定 5XFAD AD 模型小鼠中 MR1/MAIT 细胞轴对免疫和突触蛋白的贡献。研究方法我们将5XFAD小鼠与MR1缺陷小鼠(缺乏MR1和MAIT细胞)杂交。在野生型小鼠、MR1KO小鼠、5XFAD小鼠和5XFAD/MR1KO小鼠2、4、6和8月龄时,对其海马和皮层脑组织进行Western印迹分析。使用针对 GFAP(星形胶质细胞)、补体 C3 和突触后密度蛋白 (PSD)95 的抗体分析蛋白质水平。此外,还对 5XFAD 小鼠进行了新物体识别、开阔地和巴恩斯迷宫行为测试,以测量记忆缺陷。结果显示海马和皮层的结果具有区域特异性。与5XFAD小鼠相比,5XFAD/MR1KO小鼠在6-8月龄时海马中PSD95和C3的表达水平显著上调;在大脑皮层中,5XFAD/MR1KO小鼠的GFAP水平也显著升高。最后,与野生型 C57BL/6 小鼠相比,5XFAD 小鼠表现出记忆缺陷。结论和潜在影响:大约有 670 万美国人患有注意力缺失症。预计到 2050 年,这一数字将翻一番。由于目前还没有任何针对注意力缺失症的治疗方法,因此需要寻找治疗靶点作为新型治疗范例的一部分。我们的研究结果表明,MR1/MAIT细胞轴对突触后蛋白以及由此引起的AD病理产生了影响。因此,了解该轴的贡献有助于揭示先天性免疫在AD中的作用,并有可能成为AD患者未来的治疗靶点。
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引用次数: 0
Assessing Skin Sympathetic Nerve Activity and Cardiac Effects in Patients with Gastric Electrical Stimulation 评估胃电刺激患者的皮肤交感神经活动和心脏效应
Pub Date : 2024-01-11 DOI: 10.18060/27905
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.
背景:胃电刺激(GES)是胃瘫患者的一种疗法,可减轻恶心、呕吐和胃排空不良等症状。胃肠电刺激疗法的治疗效果被认为源于自律神经活动的变化,尤其是通过迷走神经的副交感神经活动。本研究通过检查皮肤交感神经活动(SKNA)来评估自律神经爆发,研究 GES 对神经活动和心脏功能的影响。方法:在三个位置记录 48 名患者的 SKNA 信号:颈部左侧(SKNA1)、颈部右侧(SKNA2)以及通过胸前心电图导联 1(SKNA3)。信号经过带通滤波(500 Hz 至 1000 Hz),以消除心电图和肌肉伪影,突出神经活动。使用 Labchart 软件计算每个 100 毫秒样本的绝对值积分 (iSKNA),并将结果导出到 Excel。在不同的 GES 条件下收集数据:GES 开启、½ 电压下的 GES、GES 关闭和 GES 重新开启。神经活动爆发的阈值是每个部分的 iSKNA 值的平均值+2 倍标准偏差。结果:aSKNA 平均值直方图显示,GES 关闭时神经活动减少。在 GES 完全开启或关闭的情况下,SKNA1 上的左侧和迷走神经活动明显低于 GES 在 ½ 电压下的活动。在 SKNA1 或 SKNA2 的变异性或平均 aSKNAs 方面未观察到其他明显差异。未来方向和潜在影响:iSKNA 数据的突发分析将解决关键问题。不同 GES 条件下爆发活动的变化可阐明 GES 对胃痉挛的治疗效果。随后将数据分为症状缓解和症状未缓解的患者,可以揭示爆发活动与疗效之间的关系。此外,猝发数据与心率变异性分析的相关性将有助于深入了解 GES 对心脏功能的影响。这项研究将增进我们对 GES 效果和安全性的了解,从而改善患者的预后。
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引用次数: 0
Fracture-Induced Effects on the Onset & Progression of Alzheimer’s Disease 骨折对阿尔茨海默病发病和进展的影响
Pub Date : 2024-01-11 DOI: 10.18060/27875
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.
阿尔茨海默病和相关痴呆症(AD/ADRD)是一种多因素、高度异质性和复杂的年龄依赖性疾病,严重影响记忆和认知功能,影响着全球近 3560 万人。在老年人中,痴呆症会使跌倒和骨折的风险增加 2-3 倍,部分原因是神经血管不稳定、原有的骨质疏松症导致骨质密度低,以及恶病质和/或肌肉疏松症导致支撑关节的肌肉组织不良。虽然AD/ADRD导致的骨折已被充分记录在案,但骨折与AD/ADRD发病或进展之间的关联却未被充分重视,因此需要进行更多的研究。我们旨在研究骨折愈合作为 AD/ADRD 发病诱因的机制作用。将四个月大、雄性、5xFAD(AD 模型)和野生型对照(C57BL/6)小鼠分为两组:手术诱发股骨骨折组和未受伤小鼠组。手术前,小鼠接受了AD行为基线测试,包括:Y迷宫中的自发交替、开阔地中的光-暗探索和主动回避实验。小鼠每周接受一次 X 射线成像,以监测骨折愈合进展和纵向注意力缺失行为测试。手术后 22 周,小鼠将被安乐死,并收集股骨和大脑。股骨将接受uCT成像、骨愈合组织学评估和炎症标志物免疫组化评估。大脑将进行组织学和神经炎症标志物分析,包括Aβ斑块沉积、tau缠结、神经元存活、神经发生以及小胶质细胞和星形胶质细胞的活化/增殖。研究结束时,我们预计 5xFAD 实验组的神经炎症标记物会增加,骨折愈合也会延迟。我们预计,与未受伤的对照组相比,股骨骨折会导致认知能力下降、Aβ积累/神经变性、神经炎症增加和血管损伤。我们预计骨折与AD恶化之间存在相关性。我们希望通过揭示这种关系的内在机制来指导未来的研究,从而开发出更强大的治疗方法。
{"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}
引用次数: 0
Student Perceptions of Two Preclinical Medical School Exam Feedback Approaches 学生对两种医学院临床前考试反馈方法的看法
Pub Date : 2024-01-11 DOI: 10.18060/27851
Elsie Gasaway, Valerie O’Loughlin
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.
背景:医学院要求学生在短时间内学习大量信息,因此有必要在终结性评估(即单元考试)后向学生提供有价值的反馈。印第安纳大学医学院(IUSM)的医科一年级学生首先学习的课程是 "人体结构"(HS),然后是 "从分子到细胞和组织"(MCT)。这两门课程提供了不同形式的考试反馈,导致学生对反馈的偏好和效用产生了轶事评论。本研究采用定性研究方法,考察布卢明顿国际大学学生对考试反馈形式的实用性和适用性的看法。研究方法:五名美国加州大学伯明顿分校二年级医学生参加了一个焦点小组,讨论他们对 HS 和 MCT 考试反馈的使用情况和感知有用性。专题分析用于解释焦点小组的数据。这项研究被 IU-IRB (19409) 认为是豁免研究。研究结果主题分析显示,学生的讨论分为三类:后勤、利用和心态。这些类别被进一步细分为主题和次主题,揭示出 13 个独特的代码。学生们花了大量时间讨论考试反馈的后勤问题。利用考试反馈的障碍包括反馈会议上提供的信息不足,以及反馈会议的时间安排不足。学生们更喜欢 MCT 考试反馈方法,但他们认识到 HS 课程的后勤工作可能会阻碍类似方法的采用。学生对如何改进两门课程的反馈提出了一些小建议。结论/意义:这些数据表明,国际医学科学院医学院一年级课程提供考试反馈的方式稍作改变,学生就会从中受益。改进措施可以包括延长考试复习课的时间,纳入对常见考试遗漏概念的讨论,为错误和正确答案提供答案解释,以及将全州范围的复习过渡到由校园主导。
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引用次数: 0
Energizing the Lung Vasculature in the Premature Infant to Promote Alveolar Formation 激活早产儿肺血管以促进肺泡形成
Pub Date : 2024-01-11 DOI: 10.18060/27774
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。
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引用次数: 0
Celiac Disease in Medical Curriculum 医学课程中的乳糜泻
Pub Date : 2024-01-11 DOI: 10.18060/27966
Elizabeth Kerns, Polly R. Husmann, PhD
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.
简介:乳糜泻是一种常见的自身免疫性疾病: 乳糜泻是一种常见的自身免疫性疾病,由摄入谷物(如小麦、大麦和黑麦)中所含的蛋白质麸质引起。 乳糜泻可在几乎所有身体系统中表现出多种症状,但大多数乳糜泻患者表现为亚临床症状。 尽管检测费用相对低廉,治疗方法也很有效(即无麸质饮食),但大多数乳糜泻患者仍未被诊断出来,从而造成了巨大的疾病负担。 研究表明,医生对乳糜泻知之甚少,这可能是导致高漏诊率的原因之一。 本研究旨在评估学生在临床前医学教育中遇到的有关乳糜泻的信息。方法: 从最近的文献中汲取信息,为临床前医学生的课程和教育资源中有关乳糜泻的介绍创建了一个评估标准。 评估的类别包括患病率、发病率/死亡率、表现、合并症和检查建议。 该评分标准用于评估美国一所大型医学院的课程和医学生常用的商业资源《USMLE 第一步急救》。结果显示 医学院课程的总体得分高于《First Aid》(分别为 31/48 和 12/48)。 除发病率/死亡率外,该课程在所有类别中的得分也较高。 该课程主要在发病率/死亡率和测试建议方面存在不足。 急救在所有类别中都存在不足。讨论 结果显示,医学院课程提供了有关乳糜泻多个方面的更完整信息。 急救 "并没有彻底解决用评分标准评估的任何类别问题。 虽然《急救》可能是对第 1 步教材的有效整合,但它很可能侧重于 "应试教育",而不是为未来的医生提供全面的医学教育。 医学课程是学生了解乳糜泻的更全面的资源。
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引用次数: 0
Blood Culture Contamination Rates in Bloomington, Association with Patient History 布卢明顿的血培养污染率与患者病史的关系
Pub Date : 2024-01-11 DOI: 10.18060/27781
Vanessa Schwieterman, Aimee Lee, Christine Motzkus
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。
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引用次数: 0
The Relationship Between Intensive Care Unit (ICU) Delirium Severity and 2-Year Mortality 重症监护室(ICU)谵妄严重程度与两年死亡率之间的关系
Pub Date : 2024-01-11 DOI: 10.18060/27869
Rachel Lehman, Samreen Jawaid, H. Lindroth, Jared W Meeker, Anthony J. Perkins, Sophia Wang, Sujuan Gao, Sikandar Khan, Babar A. Khan
Background:Delirium is an acute brain dysfunction characterized by altered cognition, attention, and level of consciousness. The presence of delirium is associated with increased risk of mortality, neurocognitive decline, and physical impairment; however, the role of ICU delirium severity in long-term health outcomes is less understood. Objective:Characterize the relationship between delirium severity and mortality risk in ICU survivors 2-years after discharge. Methods:A secondary analysis was performed on patient data collected in two randomized controlled trials (Pharmacological Management of Delirium and Deprescribing in the Pharmacologic Management of Delirium, 2009-2015). Participants received delirium assessments twice daily during hospitalization via the Confusion Assessment Method for the ICU (CAM-ICU-7). Patients enrolled at Eskenazi Hospital with complete mortality data were included in this study. Mean delirium severity was categorized as rapidly resolving (0-2), mild to moderate (2.1-5), or severe (>5). Cox proportional hazard model was used to quantify mortality risk associated with delirium severity. Analyses were adjusted for patient demographics, comorbidities, and severity-of-disease. Results:The cohort (n=434) was 54.6% female and 48.6% African American with an average age of 59.8 (SD 16.4). The admission diagnosis was acute respiratory failure/sepsis in 47.9% of patients across medical (n=272), progressive (n=52), and surgical (n=110) ICU types. Approximately one third of the original cohort (n=143) died within 2 years of index discharge. In the multivariate analysis, patients with severe delirium (>5) had nearly twice the adjusted hazard ratio for 2-year mortality compared to patients with mild-moderate delirium (aHR 2.1 [95% CI, 1.3-3.4] and aHR 1.1 [95% CI, 0.7-1.6], p=0.008). Conclusion:Severe delirium during ICU stay was significantly associated with increased 2-year mortality risk in comparison to mild-moderate (subsyndromal) delirium. Impact:The relationship between delirium severity and 2-year mortality underscores the need for further research on the mechanisms underlying ICU delirium and specific interventions to improve long-term outcomes.
背景:谵妄是一种急性脑功能障碍,以认知、注意力和意识水平的改变为特征。谵妄的存在与死亡率、神经认知功能衰退和身体损伤风险的增加有关;然而,人们对重症监护室谵妄严重程度在长期健康结果中的作用了解较少。目的:描述 ICU 存活者出院 2 年后谵妄严重程度与死亡风险之间的关系。方法:对两项随机对照试验(谵妄的药物治疗和谵妄药物治疗中的处方,2009-2015 年)中收集的患者数据进行二次分析。参与者在住院期间每天两次通过重症监护室意识混乱评估方法(CAM-ICU-7)接受谵妄评估。本研究纳入了在埃斯肯纳兹医院住院并有完整死亡率数据的患者。谵妄的平均严重程度分为快速缓解(0-2)、轻中度(2.1-5)或重度(>5)。采用 Cox 比例危险模型量化与谵妄严重程度相关的死亡风险。分析根据患者的人口统计学特征、合并症和疾病严重程度进行了调整。结果:研究对象(n=434)中女性占 54.6%,非裔美国人占 48.6%,平均年龄为 59.8 岁(SD 16.4)。入院诊断为急性呼吸衰竭/败血症的患者占 47.9%,分别属于内科(n=272)、进展期(n=52)和外科(n=110)重症监护病房类型。原始队列中约有三分之一的患者(n=143)在指标出院后两年内死亡。在多变量分析中,与轻度-中度谵妄患者相比,重度谵妄患者(>5)的2年死亡率调整后危险比几乎是轻度-中度谵妄患者的两倍(aHR 2.1 [95% CI, 1.3-3.4] 和 aHR 1.1 [95% CI, 0.7-1.6], p=0.008)。结论:与轻度-中度(亚谵妄)谵妄相比,ICU住院期间的严重谵妄与2年死亡风险的增加显著相关。影响:谵妄严重程度与2年死亡率之间的关系突出表明,有必要进一步研究ICU谵妄的内在机制以及改善长期预后的具体干预措施。
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引用次数: 0
Analysis of Lung Cancer Disparities in Northwest Indiana 印第安纳州西北部肺癌差异分析
Pub Date : 2024-01-11 DOI: 10.18060/27745
Kyra Colston, Mia Ndama, Amy Han
Background and Hypothesis: Lung cancer is the first leading cause of cancer death worldwide (~1.8 million deaths pa.). Low-Dose Computed Tomography (LDCT) screening is a preventative measure to diagnose lung cancer at an early stage, which increases the chance of survival. Northwest Indiana is a diverse region (830,000 pop.) that faces unique challenges to equitable health outcomes and access to preventative treatments, particularly within minoritized communities from a low socioeconomic status. We investigated whether the vulnerable populations of Northwest Indiana have a higher incidence of lung cancer, low LDCT screening rates, and a late stage of diagnosis, in order to identify potential gaps in healthcare access and delivery. Methods: We used LDCT screening (n = 2,481), lung cancer incidence (n = 268) and staging (n = 257) data from ZIP Codes of six cities/towns in Northwest Indiana, provided by an urban hospital system in Northwest Indiana between 2018 and 2023. The cities/towns were grouped into ‘lower’ and ‘upper’ income according to median household income level reported by 2020 U.S. census data. Chi-Squared tests were used to determine significance. Results: There is no significant difference in the incidence of lung cancer between upper and lower income cities/towns (p= 0.163). However, there is a significant difference in stage I, II, and IV diagnoses between the two income groups (p = 0.021, 0.007, and 0.013 respectively), which demonstrates an inverse relationship between income level and stage of diagnosis. The lower income group is diagnosed at a younger age (p = 0.02) with advanced stage lung cancer, despite similar rates of lung cancer incidence. Conclusion and Potential Impact: Barriers to screening for vulnerable populations in urban areas include patient-provider mistrust, health illiteracy, and lack of healthcare services. Late stage diagnosis necessitates the development of local interventions to increase early screening.
背景与假设:肺癌是全球第一大癌症死因(每年约 180 万人死亡)。低剂量计算机断层扫描(LDCT)筛查是一种预防性措施,可在早期诊断出肺癌,从而提高存活几率。印第安纳州西北部是一个多样化的地区(83 万人口),在公平健康结果和获得预防性治疗方面面临着独特的挑战,尤其是在社会经济地位较低的少数民族社区。我们调查了印第安纳州西北部的弱势人群是否肺癌发病率较高、LDCT 筛查率较低以及诊断阶段较晚,以确定在医疗保健的获取和提供方面可能存在的差距。研究方法我们使用了印第安纳州西北部一个城市医院系统提供的 2018 年至 2023 年期间印第安纳州西北部六个市/镇邮政编码的 LDCT 筛查(n = 2,481 例)、肺癌发病率(n = 268 例)和分期(n = 257 例)数据。根据 2020 年美国人口普查数据报告的家庭收入中位数水平,这些市/镇被分为 "低收入 "和 "高收入 "两组。采用 Chi-Squared 检验来确定显著性。结果高收入和低收入城市/城镇之间的肺癌发病率没有明显差异(P= 0.163)。然而,两个收入组别之间的 I 期、II 期和 IV 期诊断率存在明显差异(p 分别为 0.021、0.007 和 0.013),这表明收入水平与诊断阶段之间存在反向关系。尽管肺癌发病率相似,但较低收入群体确诊肺癌晚期的年龄较小(p = 0.02)。结论和潜在影响:城市地区弱势人群接受筛查的障碍包括患者与医疗服务提供者之间的不信任、健康文盲以及医疗服务的缺乏。晚期诊断需要当地制定干预措施,以提高早期筛查率。
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