BACKGROUND A subarachnoid hemorrhage (SAH) is a bleed into the subarachnoid space surrounding the brain. This disease affects roughly 30,000 Americans each year and approximately one in six affected individuals die at the time of the ictal event. Individuals that do survive suffer from many complications including delayed cerebral vasospasm (DCV), cerebral edema, fever, and increased intracranial pressure (ICP) amongst others. These patients often suffer from brain damage due to neuronal apoptosis as a consequence of excess neuroinflammation. Microglia, the resident macrophage of the central nervous system, and Toll-like Receptor-4 (TLR4), a pro-inflammatory transmembrane receptor, have both been shown to play a role in the neuroinflammation seen in SAH. RBC components have been shown to activate microglial TLR4, and this event is suggested to trigger downstream mechanisms leading to neuronal apoptosis. The presented research takes a closer look at the role of microglial TLR4 in early neuronal apoptosis seen in an SAH model. METHODS All mice used were 10- to 12-week-old males on a C57BL/6 background: TLR4−/−, MyD88−/−, TRIF−/− and wild type (WT). To induce an SAH, a total of 60 ul of arterial blood from a donor WT mouse was injected for over 30 seconds into another mouse. For in vitro experiments, either primary microglia (PMG) or murine microglial BV2 cells were used. Microglia were separated from murine neuronal HT22 cells by 3um cell culture inserts or transwells, before being stimulated with lipopolysaccharide (LPS), red blood cells (RBCs), or RBC components including hemin (structurally similar to heme) and hemoglobin. In vivo samples were studied using either immunohistochemistry (IHC) or Fluorescence Activated Cell Sorting (FACS), and in vitro cells were studied using IHC and Light Microscopy. Neuronal cell death was measured using TUNEL and/or FloroJade C (FJC) assays. Cognitive function after SAH was measured using the Barnes Maze protocol. RESULTS In a 24-hour time course, more death occurred in the HT22 cells associated with BV2s treated with RBCs for 12-hour and 24-hour incubation time points as compared to 1-hour and 3-hour time points. Similar results were seen in the WT PMGs, as HT22 apoptosis increased in the RBC treated WT groups as the incubation time points increased. The WT PMG and MyD88−/− RBC treated PMGs showed significant death as compared to a WT untreated control (p<0.05) using a FJC assay, and both showed more death in a TUNEL assay as compared to an untreated control. WT mice treated with whole blood and hemoglobin had significantly more apoptosis as compared with a normal saline (NS)-treated control mouse (p<0.05). WT PMGs treated with whole blood and hemoglobin had more apoptosis as compared with an untreated control. MyD88-/- treated with RBC, hemoglobin, and hemin had more HT22 cell death compared with other genotypes treated with the same component. For the Barnes Maze, TLR4−/− mice performed significantly less total errors than WT mice on POD5 and 6 (p<0.01), and took significantly less time to reach the goal chamber on POD4, POD5 (p<0.05), and POD6 (p<0.01). CONCLUSION Our experimental results suggest that a microglial TLR4-dependent, MyD88-independent pathway is involved in neuronal apoptosis very early in an SAH model via RBC and hemoglobin activation, and that neuronal cell apoptosis due to TLR4 expression may be related to SAH-related cognitive and behavioral deficits. Our results suggest that TRIF may be the intracellular adaptor that is involved in this mechanism, but further experiments are needed to confirm this.

京都大学 / 新制・論文博士 / 博士(医学) / 乙第13514号 / 論医博第2264号 / 新制||医||1061(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 萩原 正敏, 教授 湊谷 謙司, 教授 中島 貴子 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DFAM

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A recurring theme in the literature is that simulation is a positive teaching strategy when compared to other methods of instruction and produces positive student outcomes (Jefferies, 2016). Simulation provides educators a way to reproduce a clinical teaching experience in a safe, supportive learning environment. The purpose of this quantitative research study was to determine whether an obstetrical simulation educational experience is an effective strategy for educating undergraduate nursing students in the management of a postpartum hemorrhage. A quasi-experimental study using a pre-test and post-test design was employed in a Women’s Health Course and Pediatrics course over one semester. A single convenience sample (N=81) of junior baccalaureate nursing students was used for this study. There were 41 students in the control group and 40 in the experimental group. Both the control and experimental groups received the traditional didactic session, case study, skills lab instruction, and clinical. In addition, the experimental group received the postpartum simulation. This simulation study tested the differences in knowledge, satisfaction, and confidence level between junior nursing students who did and did not participate in the simulation. There were three instruments used during this study; a pre-test/post-test for knowledge acquisition, the National League for Nursing (NLN) (2005) student satisfaction and confidence level survey, and the Creighton Competency Evaluation Instrument (C-CEI) (Todd, Manz, Hawkins, Parsons, & Hercinger, 2008). The pre-test/post-test measured the knowledge acquisition obtained from the didactic session. NLN (2005) student satisfaction and confidence level survey measured students’ satisfaction and confidence level from either the interactive skills lab sessions or the simulation. The C-CEI tool measured the students’ performance during the simulation. There were four categories: assessment, communication, clinical judgment, and patient safety that the researcher measured the students’ performance during the simulation. Data for the knowledge acquisition, revealed both the experimental and control groups significantly increased between the pre-test and the post-test. The post-test showed statistically significant differences between groups, with the control group outperforming the experimental group. As such, the data demonstrate that the simulation did not have a significant effect on knowledge. Data from the NLN (2005) student satisfaction and confidence level survey were analyzed using a two group MANOVA. Although the results of the MANOVA were not significant, as a follow up analysis, the individual questions were used as the dependent variables in a MANOVA. When the individual questions were used as the dependent variables in a MANOVA, the experimental group performed significantly better in two out of the five questions on student satisfaction and five out of the nine questions on student self-confidence. There was a strong positive correlation between satisfaction with current learning and self–confidence. Data for the students’ performance were analyzed using the C-CEI tool. A perfect score on the C-CEI instrument was 14 points, 100%. The overall group average was 8.1 points or 58%. Of the four sections in the C-CEI tool, the lowest mean was Communication (0.5185), followed by Patient Safety (mean = 0.5333). Although student groups were able to communicate with the patient effectively 67% of the time, none of the simulation groups provided an organized report to the healthcare provider with minimal prompting. During the postpartum simulation, 33% of the students administered medications safely. The wrong dosage and incorrect technique were seen in 67% of the simulations. Communication and safe medication practice are essential to ensuring patient safety; it is important that faculty prepare nursing graduates to provide safe care. Even though there were limitations to this study, a convenience sample at one public university, the findings are informative and have implications for future teaching and learning strategies. The results of this study add to the body of knowledge that supports the use of simulation as a teaching strategy in undergraduate nursing education. / Educational Leadership

Obstetric hemorrhage is one of the most common causes of maternal morbidity and mortality. The measurement of quantitative blood loss (QBL) at delivery prevents clinicians from failing to recognize hemorrhage in healthy obstetric patients who initially compensate for excessive blood loss. The purpose of this project was to improve the compliance of labor and delivery nurses in a community hospital with consistent QBL measurement. Key theories that formed the basis for the project were Lewin's theory of planned change and homeostasis. The project question addressed was: Is the use of weekly scorecards to provide feedback to nurses with both blinded individual data and aggregate unit data associated with an increase in the percent of patients with blood loss at delivery documented as a QBL measurement over a 12-week period of time? A blinded scorecard of the percent of deliveries attended by each nurse that had QBL documented and an aggregate run chart of the percent of all deliveries with QBL documented were posted in the unit weekly. The postings included discussions of means to enhance facilitators of and decrease barriers to QBL measurement. Over 12 weeks, the percent of deliveries with QBL documented increased from 22.7% to 80.0%. This result is consistent with previous reports that clear and objective feedback from scorecards is associated with improvement in performance. Scorecard feedback may be explored to determine if it is associated with improvement of other nursing practices. This project has implications for positive social change as it may contribute to a reduction in preventable maternal deaths. Decreasing maternal morbidity and mortality supports the health of women in a population and influences the health of the next generation.

Diss. (sammanfattning) Stockholm : Karol. inst., 2003. / Härtill 6 uppsatser.

Diss. (sammanfattning) Linköping : Linköpings universitet, 2004. / Härtill 5 uppsatser.