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Prevalence of Positive Urine Drug Screen for Fentanyl and its Analogs in Indianapolis 印第安纳波利斯芬太尼及其类似物尿液药物筛查阳性率
Pub Date : 2024-01-11 DOI: 10.18060/27843
Jennifer Beckman, Elizabeth Mast, David Shepherd, Michelle K. Zimmerman, Rejwi Dahal
Background and Hypothesis: IU Health Pathology Laboratory (IUHPL) recently added qualitative fentanyl screening to its test menu. However, fentanyl screening is not currently part of the urine drugs of abuse (DAU) panel which includes amphetamine, barbiturates,benzodiazepines, buprenorphine, cannabinoids, methadone, cocaine, opiates, oxycodone, and phencyclidine. Since fentanyl screen is a standalone test, we were interested in determining how often specimens had this ordered in conjunction with the DAU, as we suspected not all of them did. Our hypothesis was that positive urine drug screens may also be positive for fentanyl/fentanyl analogs. Project Methods: Urine specimens sent for routine drug screens at IU Health Arnett, Ball, Bloomington, and IUHPL between June and mid-July 2023 were subjected to fentanyl screening. Specimen that screened positive were confirmed by LC-MS/MS for presence offentanyl and norfentanyl. Additionally, specimens were tested for 4ANPP (fentanyl precursor) and xylazine; if they were positive for either, they were sent to an outside laboratory to ascertain if other fentanyl analogs or designer opioids were present. Results: Of the 1,893 DAU specimens received, 51.2% were positive for at least one drug class. Only 28 had an associated fentanyl screen order. Cannabinoids represented the most prevalent drug class with a 26.7% positivity rate. Only 1,724 samples were available to screen for fentanyl as part of this study. Of these, 214 specimens were positive for fentanyl, with a positivity screen rate of 12.4%. Confirmatory testing by LC-MS/MS indicated 206 of the 214 were true positives. Conclusion and Impact: These results highlight the need for fentanyl testing and continued clinician education to increase awareness about the inability of standard urine drug screens to detect fentanyl. Dialogue between patients and clinicians would potentially decrease overdoses and/or result in more treatment referrals. Additionally, integrating fentanyl screening into the DAU panel will facilitate qualitative fentanyl testing.
背景与假设:IU 健康病理实验室(IUHPL)最近在其检验菜单中增加了芬太尼定性筛查。然而,芬太尼筛查目前并不属于尿液滥用药物(DAU)检测项目,该项目包括苯丙胺、巴比妥类药物、苯二氮卓类药物、丁丙诺啡、大麻类药物、美沙酮、可卡因、阿片剂、羟考酮和苯环利定。由于芬太尼筛查是一项独立的检测项目,我们有兴趣确定标本在进行 DAU 检测的同时进行芬太尼筛查的频率,因为我们怀疑并非所有标本都进行了芬太尼筛查。我们的假设是,尿液药物筛查阳性也可能是芬太尼/芬太尼类似物阳性。项目方法:对 2023 年 6 月至 7 月中旬期间送往 IU Health Arnett、Ball、Bloomington 和 IUHPL 进行常规药物筛查的尿液标本进行芬太尼筛查。筛查呈阳性的标本通过 LC-MS/MS 确认是否含有芬太尼和诺芬太尼。此外,还对标本进行了 4ANPP(芬太尼前体)和异丙嗪检测;如果其中任何一种检测结果呈阳性,则将标本送至外部实验室,以确定是否存在其他芬太尼类似物或特制阿片类药物。结果:在收到的 1,893 份 DAU 标本中,51.2% 的标本至少对一种药物呈阳性反应。只有 28 份样本有相关的芬太尼筛查指令。大麻类是最常见的毒品类别,阳性率为 26.7%。作为本研究的一部分,只有 1724 份样本可用于芬太尼筛查。其中 214 份样本的芬太尼检测结果呈阳性,阳性筛查率为 12.4%。通过 LC-MS/MS 进行的确认测试表明,214 份样本中有 206 份样本呈阳性。结论和影响:这些结果凸显了对芬太尼检测的需求,以及继续开展临床医生教育以提高对标准尿液药物筛查无法检测芬太尼的认识的必要性。患者和临床医生之间的对话将有可能减少过量用药和/或导致更多的治疗转介。此外,将芬太尼筛查纳入 DAU 面板将促进芬太尼定性检测。
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引用次数: 0
Retrospective Analysis of Suicide Deaths in Allen County Indiana, 2013 – 2022 2013-2022年印第安纳州艾伦县自杀死亡回顾分析
Pub Date : 2024-01-11 DOI: 10.18060/27783
Kathleen Sherman, Aaron Williams, Jana Sanders, Thomas Gutwein
Suicide rates at a national and state level have been on the rise over the past two decades. Patterns observed at the local level is less understood and underrepresented in research. Since local government can have a large impact on resource allocation in a community, revealing local suicide patterns could help facilitate targeted preventative efforts for at-risk populations. This study aims to analyze demographic patterns observed in Allen County suicides from 2013 –2022, focusing on age groups and education attainment. Data collection was completed on the 604 individuals who died by suicide in Allen County over the past decade. The collection process included documenting various demographics accessed through death certificates and coroner’s files. Within the county, suicide numbers increased over the decade. Results showed that males represented more than a 3:1 ratio of total suicides, a gunshot wound was the method of injury for 53% of all suicides, and decedents with a high school degree or less represented 62% of suicides within the population. These results echo what research has shown at the national level. Additionally, the 20-34 and the 35-54 age groups produced the greatest number of suicides consistently over the 10 years, and these suicides occurred most often in late spring and early summer. Within the 20-34 age group, individuals were more likely to commit suicide by gunshot wound (p = 0.000133). Decedents of minority ethnic and racial groups had lower education attainment compared to non-Hispanic (p = 0.000027) or white (p = 0.003314) individuals. This information could be provided to local schools with the hopes of implementing more targeted preventative measures for at-risk groups. Knowledge of suicide patterns in healthcare could lead to improved care for patients. Finally, public health entities can use these findings to adapt current health initiates to fit the needs of Allen County.
过去二十年来,全国和各州的自杀率一直呈上升趋势。在地方层面观察到的自杀模式却鲜为人知,在研究中的代表性也不足。由于地方政府会对社区的资源分配产生很大影响,因此揭示地方自杀模式有助于促进针对高危人群的预防工作。本研究旨在分析艾伦县 2013-2022 年间自杀事件中观察到的人口统计模式,重点关注年龄组和受教育程度。在过去十年中,艾伦县共有 604 人死于自杀,数据收集工作已经完成。收集过程包括通过死亡证明和验尸官档案记录各种人口统计数据。在该县,自杀人数在过去十年中有所增加。结果显示,男性占自杀总人数的比例超过了 3:1,53% 的自杀者的伤害方式是枪伤,高中或以下学历的死者占自杀总人数的 62%。这些结果与全国范围内的研究结果一致。此外,在过去 10 年中,20-34 岁和 35-54 岁年龄组的自杀人数一直最多,而且这些自杀事件多发生在春末夏初。在 20-34 岁年龄组中,更有可能发生枪伤自杀(p = 0.000133)。与非西班牙裔(p = 0.000027)或白人(p = 0.003314)相比,少数民族和种族群体的死者受教育程度较低。这些信息可以提供给当地学校,希望能为高危人群实施更有针对性的预防措施。了解医疗保健领域的自杀模式可以改善对患者的护理。最后,公共卫生机构可以利用这些发现来调整当前的卫生举措,以适应艾伦县的需求。
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引用次数: 0
Elevated Psychiatric Comorbidities in Patients with Low-risk Chest Pain Presenting in The Emergency Department 急诊科就诊的低风险胸痛患者精神疾病合并症增加
Pub Date : 2024-01-11 DOI: 10.18060/27776
Linh Dang, Kurt Kroenke, Timothy Stump, Patrick O. Monahan, J. Connors, Yelena Cherynak, Paul Musey
Background/Objective: Low-risk chest pain (LRCP), i.e. chest pain that does not pose an imminent risk or have a cardiovascular cause, constitutes the majority (80%) of cases of chest pain presenting to the emergency department (ED). Past research shows that in patients withLRCP without a history of cardiovascular disease, many will meet criteria for panic or generalized anxiety disorder. The purpose of this project is to examine the psychiatric comorbidities of patients with LRCP including differences by severity of anxiety. Methods: Baseline data collected in the Patient-Centered Treatment of Anxiety after Low-Risk Chest Pain in the Emergency Room (PACER) study were analyzed to determine: the rates of depression, somatization, posttraumatic stress disorder (PTSD), disability, and low self-efficacyin relation to increasing levels of anxiety (low anxiety but positive for panic disorder vs moderate vs severe anxiety). Also, anxiety severity groups are compared for demographic and other patient characteristics to identify potential predictors of anxiety severity. Results: In 265 patients with LRCP who screened positive for panic disorder and/or generalized anxiety disorder, the proportion with low, moderate and severe anxiety symptoms was 9%, 44% and 47%, respectively. Overall, 57% (n=150) also screened positive for depression, 54%(n=144) for somatization syndrome, and 56% (n=149) for PTSD. Rates of depression, somatization, PTSD, and disability increased as the level of anxiety increased. Compared to patients with low to moderate anxiety, patients with severe anxiety were more likely to have depression (odds ratio = 3.0), somatization (OR = 2.7), PTSD (OR = 2.6), disability (OR = 2.4), and low self-efficacy (OR = 3.5). Conclusion and Potential Implications: Patients with LRCP and anxiety are likely to have other psychiatric comorbidities. Additionally, as rates of comorbidities increase with the anxiety severity, detection and management of anxiety is essential to provide optimal care for low-riskchest pain.
背景/目的:在急诊科 (ED) 就诊的胸痛病例中,大多数(80%)是低风险胸痛 (LRCP),即不构成紧迫风险或没有心血管原因的胸痛。过去的研究表明,在没有心血管疾病史的 LRCP 患者中,许多人符合恐慌症或广泛性焦虑症的标准。本项目旨在研究 LRCP 患者的精神合并症,包括焦虑严重程度的差异。研究方法对急诊室低风险胸痛后焦虑症患者中心治疗(PACER)研究中收集的基线数据进行分析,以确定:抑郁、躯体化、创伤后应激障碍(PTSD)、残疾和自我效能低的发生率与焦虑程度的增加(低度焦虑但惊恐障碍阳性 vs 中度 vs 重度焦虑)之间的关系。此外,还比较了焦虑严重程度组的人口统计学特征和其他患者特征,以确定焦虑严重程度的潜在预测因素。结果:在筛查出惊恐障碍和/或广泛性焦虑症阳性的 265 名 LRCP 患者中,有低度、中度和重度焦虑症状的比例分别为 9%、44% 和 47%。总体而言,57%(n=150)的患者还筛查出抑郁症,54%(n=144)的患者筛查出躯体化综合征,56%(n=149)的患者筛查出创伤后应激障碍。抑郁、躯体化、创伤后应激障碍和残疾率随着焦虑程度的增加而增加。与中低度焦虑患者相比,重度焦虑患者更有可能患有抑郁症(几率比=3.0)、躯体化(OR=2.7)、创伤后应激障碍(OR=2.6)、残疾(OR=2.4)和低自我效能感(OR=3.5)。结论和潜在影响:患有 LRCP 和焦虑症的患者很可能合并有其他精神疾病。此外,由于合并症的发生率会随着焦虑严重程度的增加而增加,因此检测和管理焦虑对于为低风险胸痛患者提供最佳护理至关重要。
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引用次数: 0
Retrospective Analysis of COVID-19 Impact on Social + Emotional Development in Children of Low-Income Communities from Head Start 回顾性分析 COVID-19 对低收入社区儿童社会和情感发展的启蒙教育影响
Pub Date : 2024-01-11 DOI: 10.18060/27720
Gabrielle S. Li, Satya P. Sanapati, Amy Han
Background:Geminus Head Start is a federal program that works with children under five years old from low-income communities to promote school readiness. The organization in Northwest Indiana provided anecdotal data on delayed social and emotional development of children during the pandemic. Studies have shown that adverse childhood development can have a severe psychological and physiological impact on health outcomes into adulthood. However, there has been a lack of research on quantifying the extent of damage from the pandemic on our Head Start children, who mainly identify as Black/African American. Methods:Geminus Head Start provided demographic data including race, postal codes and DECA for over 4650 students from 2019-2023. DECA, Devereux Early Childhood Assessment, is used by educators to evaluate children’s social emotional competence for early intervention. In this study, we are investigating the DECA categories, including initiative, self-control, and attachment/relationships. We analyzed DECA scores via ANOVA along with listening into the teacher focus groups. Results:Students had increased attachment/relationship scores from the 2019-2020 school year to the 2020-2021 school year (36.69 to 44.59). However, following COVID-19 to the 2021-2022 and 2022-2023 school years, these scores dropped to 23.51. When looking at the second protective factor, self-regulation, the opposite trend was found. The scores went from 18.79 in 2019-2020 down to 14.68 in 2020-2021 and eventually up to 23.51 in 2021-2022. Conclusion:Like most institutions, the pandemic has created a time of isolation and instability for our children and their families. In particular, these children have not been able to access adequate conditions to develop emotional and social maturity. Lacking this development can lead to several negative health outcomes as it may impact mental health and the ability to create healthy supportive networks.
背景:Geminus Head Start 是一项联邦计划,旨在帮助低收入社区的五岁以下儿童做好入学准备。印第安纳州西北部的组织提供了有关大流行病期间儿童社会和情感发育延迟的轶事数据。研究表明,儿童期的不良发展会对成年后的健康产生严重的心理和生理影响。然而,关于大流行对以黑人/非洲裔美国人为主的 "启蒙儿童 "造成的损害程度的量化研究还很缺乏。方法:Geminus Head Start 提供了超过 4650 名学生 2019-2023 年的人口统计数据,包括种族、邮政编码和 DECA。DECA(德维尔儿童早期评估)被教育工作者用于评估儿童的社会情感能力,以便进行早期干预。在本研究中,我们调查了 DECA 的类别,包括主动性、自我控制和依恋/关系。我们通过方差分析对 DECA 分数进行了分析,同时听取了教师焦点小组的意见。结果:从2019-2020学年到2020-2021学年,学生的依恋/关系得分有所提高(从36.69分到44.59分)。然而,在 COVID-19 之后的 2021-2022 学年和 2022-2023 学年,这些分数降至 23.51。在研究第二个保护因素--自我调节时,发现了相反的趋势。得分从 2019-2020 学年的 18.79 分下降到 2020-2021 学年的 14.68 分,最终上升到 2021-2022 学年的 23.51 分。结论:与大多数机构一样,大流行病给我们的儿童及其家庭带来了一段孤立和不稳定的时期。特别是,这些儿童无法获得足够的条件来发展情感和社会成熟度。缺乏这种发展可能会导致一些负面的健康后果,因为它可能会影响心理健康和建立健康支持网络的能力。
{"title":"Retrospective Analysis of COVID-19 Impact on Social + Emotional Development in Children of Low-Income Communities from Head Start","authors":"Gabrielle S. Li, Satya P. Sanapati, Amy Han","doi":"10.18060/27720","DOIUrl":"https://doi.org/10.18060/27720","url":null,"abstract":"Background:Geminus Head Start is a federal program that works with children under five years old from low-income communities to promote school readiness. The organization in Northwest Indiana provided anecdotal data on delayed social and emotional development of children during the pandemic. Studies have shown that adverse childhood development can have a severe psychological and physiological impact on health outcomes into adulthood. However, there has been a lack of research on quantifying the extent of damage from the pandemic on our Head Start children, who mainly identify as Black/African American. \u0000Methods:Geminus Head Start provided demographic data including race, postal codes and DECA for over 4650 students from 2019-2023. DECA, Devereux Early Childhood Assessment, is used by educators to evaluate children’s social emotional competence for early intervention. In this study, we are investigating the DECA categories, including initiative, self-control, and attachment/relationships. We analyzed DECA scores via ANOVA along with listening into the teacher focus groups. \u0000Results:Students had increased attachment/relationship scores from the 2019-2020 school year to the 2020-2021 school year (36.69 to 44.59). However, following COVID-19 to the 2021-2022 and 2022-2023 school years, these scores dropped to 23.51. When looking at the second protective factor, self-regulation, the opposite trend was found. The scores went from 18.79 in 2019-2020 down to 14.68 in 2020-2021 and eventually up to 23.51 in 2021-2022. \u0000Conclusion:Like most institutions, the pandemic has created a time of isolation and instability for our children and their families. In particular, these children have not been able to access adequate conditions to develop emotional and social maturity. Lacking this development can lead to several negative health outcomes as it may impact mental health and the ability to create healthy supportive networks.","PeriodicalId":20522,"journal":{"name":"Proceedings of IMPRS","volume":" 19","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139626396","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
Silencing COQ8B in Aortic Smooth Muscle Cells Reveals Cellular Dysfunction Related to Changes in Cell Proliferation 沉默主动脉平滑肌细胞中的 COQ8B 可揭示与细胞增殖变化有关的细胞功能障碍
Pub Date : 2024-01-11 DOI: 10.18060/27779
Joshua Davis, Benjamin Landis
Background/Objective: Thoracic aortic aneurysm (TAA) is a prevalent disorder that predisposes to aortic dissection. Prior work identified the ubiquinone biosynthesis gene COQ8B as a genetic modifier of TAA progression. We sought to determine the impact of decreased COQ8B on global transcription in aortic smooth muscle cells (SMCs). Methods: Primary human aortic SMCs from a healthy donor were seeded in 12-well plates. Six experimental conditions were created, each with 3 replicates: 1) siRNA targeting COQ8B (siCOQ8B); 2) siRNA targeting the dominant TAA gene SMAD3 (siSMAD3); 3) negative controlsiRNA (siNeg); 4) siCOQ8B and siSMAD3; 5) siCOQ8B with Angiotensin II (AngII) stimulation (siCOQ8B+AngII); 6) siNeg+AngII. RNA was extracted approximately 48 hours post-siRNA transfection and, for AngII conditions, after 1 hour of incubation with AngII (100 nM).  mRNAsequencing was performed and downstream analysis utilized R packages EdgeR and topGO. Results: Multidimensional scaling identified distinct clustering of samples by experimental condition. Downregulated genes in siCOQ8B were enriched for Gene Ontology pathways related to cell proliferation including cell cycle regulators, DNA replication, and mitosis. MYOCD, a master regulator of SMC homeostasis, was downregulated. Similar proliferation-related pathways were enriched in siCOQ8B+siSMAD3 and siCOQ8B+AngII compared to siNeg. Pathways related to cell proliferation in siCOQ8B+AngII cells were downregulated when compared to siCOQ8B which indicates that AngII infusion in the context of COQ8B silencing may further dysregulate cell proliferation pathways. Conclusion: The results indicate that COQ8B has an important role in cell cycle processes in aortic SMCs, including when SMCs are exposed to stressors associated with TAA development. Stimulation of angiotensin receptors may exacerbate the effects of decreased COQ8B in these processes. To investigate these experimental results in human pathology, bulk RNA samples and intact nuclei have been isolated from frozen human aortic specimens and prepared for transcriptomic analysis.
背景/目的:胸主动脉瘤(TAA)是一种易导致主动脉夹层的常见疾病。先前的研究发现泛醌生物合成基因 COQ8B 是 TAA 进展的遗传修饰因子。我们试图确定 COQ8B 减少对主动脉平滑肌细胞(SMCs)全局转录的影响。研究方法将来自健康供体的原代人类主动脉平滑肌细胞播种在 12 孔板中。创建了六种实验条件,每种条件有 3 个重复:1)靶向 COQ8B 的 siRNA(siCOQ8B);2)靶向显性 TAA 基因 SMAD3 的 siRNA(siSMAD3);3)阴性对照 siRNA(siNeg);4)siCOQ8B 和 siSMAD3;5)siCOQ8B 与血管紧张素 II(AngII)刺激(siCOQ8B+AngII);6)siNeg+AngII。进行 mRNA 测序,并使用 R 软件包 EdgeR 和 topGO 进行下游分析。结果多维标度确定了不同实验条件下样本的不同聚类。siCOQ8B 中下调的基因富集于与细胞增殖相关的基因本体通路,包括细胞周期调节因子、DNA 复制和有丝分裂。SMC稳态的主调节因子 MYOCD 也被下调。与 siNeg 相比,siCOQ8B+siSMAD3 和 siCOQ8B+AngII 富集了类似的增殖相关通路。与 siCOQ8B 相比,siCOQ8B+AngII 细胞中与细胞增殖相关的通路下调,这表明在 COQ8B 沉默的情况下输注 AngII 可能会进一步导致细胞增殖通路失调。结论研究结果表明,COQ8B 在主动脉 SMC 的细胞周期过程中具有重要作用,包括当 SMC 暴露于与 TAA 发展相关的应激源时。血管紧张素受体的刺激可能会加剧 COQ8B 在这些过程中的作用。为了在人体病理学中研究这些实验结果,我们从冷冻的人体主动脉标本中分离出了大量 RNA 样本和完整的细胞核,并准备进行转录组分析。
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引用次数: 0
Ineffectiveness of mitoTEMPO on Cardiomyocyte S-phase Activity in TNNI3K-expressing Mice mitoTEMPO 对表达 TNNI3K 的小鼠心肌细胞 S 期活动无效
Pub Date : 2024-01-11 DOI: 10.18060/27848
Elias Chahoud, Sean Reuter, Loren Field
Background and Hypothesis: The limited regenerative capacity of the mammalian adult myocardium is a significant roadblock for therapeutic approaches in cardiovascular disease. Cell cycle arrest following S-phase is widely considered a primary contributor to the reduced proliferative capacity of adult cardiomyocytes. Recently, expression of troponin I-interacting kinase (Tnni3k) was shown to increase cardiomyocyte S-phase activity in mice. Tnni3k was previously shown to enhance ROS formation and adverse cardiac remodeling following injury. Our primary hypothesis was that TNNI3K-induced cardiomyocyte DNA synthesis resulted from enhanced ROS signaling. To test this, cardiomyocyte S-phase activity in TNNI3K-expressing mice was compared between those treated with the ROS scavenging agent mitoTEMPO and untreated mice. Project Methods: Transgenic mice expressing TNNI3K were subjected to 14 days infusion with mitoTEMPO (experimental group) or vehicle (control group). The mice were also subjected to 14 days infusion with bromodeoxyuridine (BrdU) to identify DNA synthesis during S-phase (all mice carried a cardiomyocyte-restricted nuclear-localized transgenic reporter to aid in cardiomyocyte nuclei identification). The proportion of cardiomyocytes in S-phase was determined and mean S-phase activity was compared between treatment groups. Ploidy analysis was also conducted to determine if cardiomyocytes completing S-phase progressed through karyokinesis. Results: The percentage of cardiomyocytes in S-phase in the control and mitoTEMPO treated group were 0.819% ± 0.163% and 0.855% ± 0.138%, respectively (mean ± SEM, p=0.873). Ploidy analysis revealed no overt difference in DNA content in S-phase-positive cardiomyocyte nuclei between the groups. Hence, we have shown that there is no appreciable difference in cell cycle induction or progression in cardiomyocytes from control vs. mitoTEMPO treated mice expressing TNNI3K. Conclusion and Potential Impact: These data suggest that (a) TNNI3K-induced cardiomyocyte S-phase activity is not secondary to elevated ROS activity, and (b) reduction of ROS activity does not relax the cell cycle block between S-phase and karyokinesis in adultcardiomyocytes.
背景与假设:哺乳动物成体心肌的再生能力有限,这是心血管疾病治疗方法的一大障碍。人们普遍认为,S 期后的细胞周期停滞是导致成体心肌细胞增殖能力下降的主要原因。最近,研究表明表达肌钙蛋白 I-互作激酶(Tnni3k)可提高小鼠心肌细胞 S 期活性。Tnni3k 以前曾被证明能增强 ROS 的形成和损伤后的不良心脏重塑。我们的主要假设是 TNNI3K 诱导的心肌细胞 DNA 合成是由增强的 ROS 信号转导引起的。为了验证这一假设,我们比较了用 ROS 清除剂 mitoTEMPO 处理的 TNNI3K 表达小鼠和未处理小鼠的心肌细胞 S 期活性。项目方法:对表达 TNNI3K 的转基因小鼠进行为期 14 天的 mitoTEMPO(实验组)或药物(对照组)输注。小鼠还需输注溴脱氧尿苷(BrdU)14 天,以鉴定 S 期的 DNA 合成(所有小鼠均携带心肌细胞限制性核定位转基因报告物,以帮助鉴定心肌细胞核)。测定处于 S 期的心肌细胞比例,并比较不同治疗组的平均 S 期活性。还进行了倍性分析,以确定完成 S 期的心肌细胞是否进行了核动分裂。结果对照组和 mitoTEMPO 治疗组处于 S 期的心肌细胞百分比分别为 0.819% ± 0.163% 和 0.855% ± 0.138%(平均值 ± SEM,P=0.873)。倍性分析显示,各组间 S 期阳性心肌细胞核中的 DNA 含量无明显差异。因此,我们已经证明,对照组与经 mitoTEMPO 处理的表达 TNNI3K 的小鼠的心肌细胞在细胞周期诱导或进展方面没有明显差异。结论和潜在影响:这些数据表明:(a) TNNI3K 诱导的心肌细胞 S 期活动并非继发于 ROS 活性的升高;(b) ROS 活性的降低并不会放松成体心肌细胞 S 期和核动期之间的细胞周期阻滞。
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引用次数: 0
Ankyloglossia and its Importance in Sustained Breastfeeding 舌尖前音及其在持续母乳喂养中的重要性
Pub Date : 2024-01-11 DOI: 10.18060/27897
Chelsea Fathauer, Danielle Tingley, Sarah Burgin
Ankyloglossia, commonly known as tongue-tie, is reported to affect 7% of infants and can impact ability to breastfeed. A comprehensive review of literature was taken which included an assessment of which diagnostic tools are most accurate in determining ankyloglossia associated with difficult breastfeeding. It was noted that there was not a standardized approachto identifying and treating ankyloglossia in breastfed infants. Based on this review, a multidisciplinary team was established to develop a team for a holistic assessment of breastfeeding efficacy. A protocol was developed for assessment of frenotomy impact on breastfeeding. It included LATCH, Coryllos Scale, and IBFAT as the most useful evaluation tools and developed a prospective assessment in infants with ankyloglossia. This study is in the early data collection phase. The goal of this study is to fill an important gap in the knowledge of the impact of ankyloglossia in sustained breastfeeding.
据报道,有 7% 的婴儿会出现舌侧畸形(俗称 "舌系带"),这会影响母乳喂养的能力。我们对文献进行了全面回顾,包括评估哪些诊断工具在确定与母乳喂养困难相关的舌系带异常方面最为准确。我们注意到,目前还没有一种标准化的方法来识别和治疗母乳喂养婴儿的舌侧畸形。在此基础上,我们成立了一个多学科小组,以建立一个全面评估母乳喂养效果的团队。为评估脐带切除术对母乳喂养的影响,制定了一项协议。该方案将 LATCH、Coryllos 量表和 IBFAT 作为最有用的评估工具,并对患有踝舌肌无力的婴儿进行了前瞻性评估。这项研究正处于早期数据收集阶段。这项研究的目标是填补有关强直性口吃对持续母乳喂养影响的重要知识空白。
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引用次数: 0
Evaluation of a Pediatric High-Flow Nasal Cannula Training Program for Providers at Moi Teaching and Referral Hospital in Eldoret, Kenya 肯尼亚埃尔多雷特莫伊教学和转诊医院儿科高流量鼻导管培训项目评估
Pub Date : 2024-01-11 DOI: 10.18060/27761
Kaitlyn A. Roberts, Emaan G. Bhutta, Adnan Bhutta, Megan S. McHenry, Polycarp Mandi, Eric Ngetich, Faith Sila, Hellen Jemeli, Sarah Kimetto, Laura J. Ruhl, Joram Nyandat, Julika Kaplan
Background: High-flow nasal cannula (HFNC) is a relatively safe, effective, and well-tolerated form of non-invasive ventilation for children with respiratory distress and is regularly used in resource-rich settings. Pediatric HFNC has been successfully implemented in resource-limited settings; however, little is known about the training process required to integrate HFNC into care. The present study evaluates a pediatric HFNC training program conducted at Moi Teaching and Referral Hospital (MTRH) in Eldoret, Kenya prior to HFNC implementation at Shoe4Africa Children’s Hospital. Methods: This study took place within the Academic Model Providing Access to Healthcare (AMPATH) program, a partnership among MTRH, Moi University, and a consortium of North American universities led by Indiana University. The training program curriculum included information about HFNC; clinical signs of respiratory distress; a demonstration and hands-on practice with HFNC machines; a locally adapted protocol for pediatric HFNC implementation; and a sample patient case. Fifty-nine acute care providers (nurses, clinical officers, medical officers, and registrars) participated in training. Participants completed pre-tests and post-tests (immediate and 3-month follow-up) containing open-ended questions to assess HFNC knowledge and five-point Likert scale questions to assess HFNC comfort and attitudes. Data were analyzed using descriptive statistics and two-proportion Z-tests (α=0.05). Results: Average knowledge assessment scores significantly increased from pre-test (2.19/6) to post-test (5.59/6; p<0.001). While scores decreased slightly at the 3-month follow-up, they remained increased from pre-test levels (4.53/6; p<0.001). The percentage of respondents who answered each knowledge assessment question correctly on the post-test and 3-month followup were significantly increased from the pre-test. Participant comfort using HFNC was increased on both the post-test (p<0.001) and 3-month follow-up (p=0.038). Conclusions: This program successfully trained providers in pediatric HFNC use at MTRH and could inform future HFNC training in resource-limited settings. Future studies should evaluate pediatric outcomes at Shoe4Africa after HFNC implementation.
背景:高流量鼻插管(HFNC)是治疗呼吸窘迫儿童的一种相对安全、有效且耐受性良好的无创通气方式,经常在资源丰富的环境中使用。小儿 HFNC 已在资源有限的环境中成功实施;然而,人们对将 HFNC 纳入护理所需的培训过程知之甚少。本研究评估了肯尼亚埃尔多雷特的莫伊教学和转诊医院(Moi Teaching and Referral Hospital,MTRH)在 Shoe4Africa 儿童医院实施 HFNC 之前开展的儿科 HFNC 培训项目。方法:这项研究是在学术模式提供医疗保健(AMPATH)计划内进行的,该计划由 MTRH、莫伊大学(Moi University)和印第安纳大学(Indiana University)牵头的北美大学联盟合作开展。培训计划课程包括有关高频核磁共振的信息、呼吸窘迫的临床表现、高频核磁共振机器的演示和实际操作、根据当地情况调整的儿科高频核磁共振实施方案以及一个病人病例样本。59 名急症护理人员(护士、临床官员、医务官员和登记员)参加了培训。参加者完成了前测和后测(即时和 3 个月随访),前测和后测包含评估 HFNC 知识的开放式问题,以及评估 HFNC 舒适度和态度的五点李克特量表问题。数据分析采用描述性统计和两比例 Z 检验(α=0.05)。结果从测试前(2.19/6)到测试后(5.59/6;p<0.001),知识评估平均得分明显增加。虽然在 3 个月的随访中得分略有下降,但与测试前的水平(4.53/6;p<0.001)相比仍然有所上升。与测试前相比,在测试后和 3 个月随访中正确回答每个知识评估问题的受访者比例都有显著提高。参加者使用 HFNC 的舒适度在测试后(p<0.001)和 3 个月随访(p=0.038)中均有所提高。结论:该项目成功培训了港铁医院儿科 HFNC 的使用,可为今后在资源有限的环境中开展 HFNC 培训提供参考。未来的研究应评估 Shoe4Africa 实施 HFNC 后的儿科治疗效果。
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引用次数: 0
Affinity Purification of Anti-Parkin Antibodies from Rabbit Serum for their Application in Immunohistochemistry 从兔血清中亲和力纯化抗帕金森抗体,以用于免疫组织化学分析
Pub Date : 2024-01-11 DOI: 10.18060/27735
Noah McMurtry, Bo Zhao
Background:Parkin is a mitochondrial autophagy protein that is associated with Parkinson’s Disease (PD), as well as auditory function. Parkin dysfunction in the context of PD allows accumulation of protein aggregates, leading to dopaminergic neurotoxicity. Previous work has demonstrated that Parkin plays an essential role in normal auditory function, as Prkn-/- mice exhibit significantly reduced hearing sensitivity. However, Prkn-/- mice also experience a protective effect from cochlear hair cell death and hearing loss caused by aminoglycosides, which are commonly used antibiotics that can cause permanent hearing loss. Multiple antibodies marketed as suitable for immunohistochemistry (IHC) have been validated using Prkn-/- tissues; however, they exhibit non-specific activity. This project aims to generate a highly specific antibody for accurate and reliable detection of Parkin expression. Project Methods:Rabbits were immunized using two Parkin peptides, notated P1 and P2, and the resulting serum was collected. A two-step purification process was utilized in this project, first isolating the IgGs from serum via protein A/G columns, and secondly using affinity purification to obtain specific antibodies against antigens P1 and P2. Additionally, two different protocols for affinity purification were tested and compared. Purity of serum, IgG, and specific antibodies was assessed by Western blot and immunofluorescence. Results:Utilizing the first purification protocol, IHC antibodies were applied in Western blot, and all demonstrated a prominent ~50kD band specific to Parkin, with some degree of nonspecific binding. Immunostaining confirmed functionality of the IHC antibodies and revealed those against P2 exhibited higher binding specificity. The second purification protocol generated IHC antibodies of similar, if not slightly superior specific interaction. Conclusion/Implications:Further investigation of Parkin expression would facilitate a better understanding of how it may be associated with the development of PD, as well as auditory function, with the potential of utilizing Parkin as a therapeutic target in PD treatment and preventing aminoglycoside ototoxicity.
背景:Parkin是一种线粒体自噬蛋白,与帕金森病(PD)以及听觉功能有关。帕金森病中的Parkin功能障碍会导致蛋白质聚集,从而引起多巴胺能神经毒性。先前的研究表明,Parkin 在正常听觉功能中起着至关重要的作用,因为 Prkn-/- 小鼠的听觉灵敏度明显降低。然而,Prkn-/-小鼠还对氨基糖苷类药物引起的耳蜗毛细胞死亡和听力损失具有保护作用,氨基糖苷类药物是一种常用的抗生素,可导致永久性听力损失。市场上销售的多种适用于免疫组织化学(IHC)的抗体已通过 Prkn-/- 组织的验证,但它们表现出非特异性活性。本项目旨在产生一种高度特异性的抗体,用于准确可靠地检测 Parkin 的表达。项目方法:使用两种 Parkin 多肽(记为 P1 和 P2)对兔子进行免疫,并收集所产生的血清。该项目采用了两步纯化过程,首先通过蛋白 A/G 柱从血清中分离出 IgG,其次使用亲和纯化获得针对抗原 P1 和 P2 的特异性抗体。此外,还对两种不同的亲和纯化方案进行了测试和比较。通过 Western 印迹和免疫荧光评估了血清、IgG 和特异性抗体的纯度。结果:利用第一种纯化方案,在 Western 印迹中应用了 IHC 抗体,所有抗体都显示出一条明显的 ~50kD 带,特异性地与 Parkin 结合,但也有一定程度的非特异性结合。免疫染色证实了 IHC 抗体的功能性,并显示针对 P2 的抗体具有更高的结合特异性。第二种纯化方案产生的 IHC 抗体具有类似的特异性相互作用,甚至略胜一筹。结论/意义:对Parkin表达的进一步研究将有助于更好地了解Parkin如何与PD的发展以及听觉功能相关联,从而有可能将Parkin作为治疗PD的靶点并预防氨基糖苷类药物的耳毒性。
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引用次数: 0
The Effects of Integrative Palliative Oncology on Health System Burden 综合姑息肿瘤学对医疗系统负担的影响
Pub Date : 2024-01-11 DOI: 10.18060/27950
Jackson Brandon, J. McCollom
Background: Early integration of palliative care in oncology has been shown to benefit patients on an individual level, especially regarding mood and quality of life. These patients both have a difficult disease course – where palliative care can help with interpersonal, spiritual, physical, and care planning concerns – and represent a substantial burden on inpatient facilities like intensive care units and emergency departments. This study explores relationships between early palliative oncology, patient healthcare experience, and broader burden on the health system.  Methods: A retrospective chart review was performed comparing oncology patients at Parkview Regional Medical Center in Fort Wayne, IN. Cohort A (200 patients) received palliative care along with standard oncology care while cohort B (200 patients) received standard oncology care alone. Post-diagnosis emergency department visits, inpatient stays, and intensive care unit stays were compared. So were in-hospital deaths, referrals to hospice, and record of advance care planning documents.  Results: Two endpoints evaluated by Chi2 analysis were statistically significant (p values <0.01): Cohort A was more likely than cohort B to be referred to hospice (79.5% vs 31.5%) and more likely to have advance care planning documents on file (38.5% vs 21%). Additionally, a T-test showed statistically significant difference (p=.001) for inpatient stays post-palliative care encounter versus patients who had no palliative care (1.75 vs 2.41).   Conclusion: This study shows correlation between integrated oncology care with patients filing ACP documents and being referred to hospice. Additionally, it finds that cancer patients who visit the palliative care office have fewer inpatient stays after their visit than those who don’t visit at all.    Future Implications: Future studies in this area should explore the latter finding from new perspectives, perhaps focusing on the differences between palliative care visit promptly after diagnosis/staging and palliative care implemented long after diagnosis/staging or not administered at all.  
背景:事实证明,将姑息关怀尽早纳入肿瘤治疗可使患者个人受益,尤其是在情绪和生活质量方面。这些患者的病程艰难,姑息关怀可以帮助他们解决人际交往、精神、身体和护理计划等方面的问题,同时也给重症监护病房和急诊科等住院设施带来了沉重负担。本研究探讨了早期肿瘤姑息治疗、病人的医疗体验和医疗系统的更广泛负担之间的关系。 研究方法对印第安纳州韦恩堡帕克维尤地区医疗中心的肿瘤患者进行了回顾性病历审查。队列 A(200 名患者)在接受标准肿瘤治疗的同时接受姑息治疗,队列 B(200 名患者)则只接受标准肿瘤治疗。对诊断后的急诊就诊率、住院时间和重症监护室停留时间进行了比较。此外,还对院内死亡、转诊至临终关怀机构以及预先护理计划文件的记录进行了比较。 结果:通过Chi2分析评估的两个终点具有统计学意义(P值小于0.01):队列 A 比队列 B 更有可能被转诊至临终关怀机构(79.5% 对 31.5%),也更有可能拥有预先医疗规划文件(38.5% 对 21%)。此外,T检验显示,接受姑息关怀后的住院时间与未接受姑息关怀的患者住院时间(1.75 vs 2.41)之间存在显著差异(p=.001)。 结论这项研究表明,肿瘤综合治疗与患者提交 ACP 文件和被转诊至临终关怀机构之间存在相关性。此外,研究还发现,到姑息关怀办公室就诊的癌症患者在就诊后的住院时间少于未就诊的患者。 未来意义:该领域的未来研究应从新的角度探讨后一项发现,或许可以重点研究在确诊/分期后立即就诊的姑息关怀与确诊/分期后很久才实施姑息关怀或根本就不实施姑息关怀之间的差异。
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引用次数: 0
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Proceedings of IMPRS
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