ゼブラフィッシュ尾びれ再生における新規分子メカニズムの研究

広島大学(Hiroshima University)博士(理学)Doctor of Sciencedoctora

mediation: R package for causal mediation analysis

In this paper, we describe the R package mediation for conducting causal mediation analysis in applied empirical research. In many scientific disciplines, the goal of researchers is not only estimating causal effects of a treatment but also understanding the process in which the treatment causally affects the outcome. Causal mediation analysis is frequently used to assess potential causal mechanisms. The mediation package implements a comprehensive suite of statistical tools for conducting such an analysis. The package is organized into two distinct approaches. Using the model-based approach, researchers can estimate causal mediation effects and conduct sensitivity analysis under the standard research design. Furthermore, the design-based approach provides several analysis tools that are applicable under different experimental designs. This approach requires weaker assumptions than the model-based approach. We also implement a statistical method for dealing with multiple (causally dependent) mediators, which are often encountered in practice. Finally, the package also offers a methodology for assessing causal mediation in the presence of treatment noncompliance, a common problem in randomized trials

Rewarming for accidental hypothermia in an urban medical center using extracorporeal membrane oxygenation.

BACKGROUND: Accidental hypothermia complicated by cardiac arrest carries a high mortality rate in urban areas. For moderate hypothermia cases conventional rewarming methods are usually adequate, however in severe cases extracorporeal membrane oxygenation (ECMO) is known to provide the most efficient rewarming with complete cardiopulmonary support. We report a case of severe hypothermia complicated by prolonged cardiac arrest successfully resuscitated using ECMO. CASE REPORT: A 45 year old female was brought to our emergency department with a core body temperature CONCLUSIONS: This case demonstrates the advantages of advanced internal rewarming techniques, such as ECMO, for quick and efficient rewarming of severely hypothermic patients. This case supports the use of ECMO in severely hypothermic patients as the standard of care

Right ventricular rupture and tamponade caused by malposition of the Avalon cannula for venovenous extracorporeal membrane oxygenation

Placement of the Avalon Elite bicaval dual lumen cannula for venovenous extracorporeal membrane oxygenation (VV-ECMO) via the internal jugular vein requires precise positioning of the cannula tip in the inferior vena cava with echocardiography or fluoroscopy guidance. Correct guidewire placement is clearly the key first step in assuring proper advancement of the cannula. We report a case of unexpected wire migration into the right ventricle at the time of final cannula advancement, resulting in right ventricular rupture and tamponade. Transesophageal echocardiography is an important monitoring modality for appropriate placement of the VV-ECMO guidewire and Avalon cannula, and in particular, for early identification of potential complications

Rigid Sternal Fixation Improves Postoperative Recovery

INTRODUCTION: During the past five years, ridged sternal fixation has been utilized for sternal closure after cardiac surgery. It is known that this procedure provides better sternal stability; however, its contribution to patient recovery has not been investigated. METHODS: Retrospective chart review was conducted for patients who underwent CABG and/or valve surgery in our institution between 2009 and 2010. Preoperative, perioperative, and follow-up data of patients with ridgid fixation (group R, n=89) were collected and compared with those patients with conventional sternal closure (group C, n=133). The decision regarding the sternal closure method was based on the surgeon\u27s preferences. Univariate followed by multivariate analyses were performed to evaluate the dominant factor of sternal lock usage and to evaluate postoperative recoveries. The factors included in the analyses were; age, sex, coronary risk factors, urgency of surgery, ejection fraction, coronary anatomy, preoperative stroke, renal function, and preoperative presence of heart failure. All statistical analyses were performed by JMP software. RESULTS: Group R was younger (62 ± 9 in group R vs 69 ± 11 in group C, p CONCLUSION: Rigid sternal fixation systems were more frequently applied to low risk young male patients. Among these selected patients, ridgid sternal fixation can contribute to early patient recovery

Ischemia-Reperfusion Injury of the Cochlea: Pharmacological Strategies for Cochlear Protection and Implications of Glutamate and Reactive Oxygen Species

A large amount of energy produced by active aerobic metabolism is necessary for the cochlea to maintain its function. This makes the cochlea vulnerable to blockade of cochlear blood flow and interruption of the oxygen supply. Although certain forms of human idiopathic sudden sensorineural hearing loss reportedly arise from ischemic injury, the pathological mechanism of cochlear ischemia-reperfusion injury has not been fully elucidated. Recent animal studies have shed light on the mechanisms of cochlear ischemia-reperfusion injury. It will help in the understanding of the pathology of cochlear ischemia-reperfusion injury to classify this injury into ischemic injury and reperfusion injury. Excitotoxicity, mainly observed during the ischemic period, aggravates the injury of primary auditory neurons. On the other hand, oxidative damage induced by hydroxyl radicals and nitric oxide enhances cochlear reperfusion injury. This article briefly summarizes the generation mechanisms of cochlear ischemia-reperfusion injury and potential therapeutic targets that could be developed for the effective management of this injury type

Sternal pain after rigid fixation: a pilot study of randomization rigid vs conventional wire closure.

Objective: Rigid sternal fixation may provide better sternal closure than conventional sternal wire closure. We performed a prospective randomized study to investigate if rigid closure reduces postoperative sternal pain. Methods: Patients undergoing CABG ± valve surgery between July 2011 and January 2012 were prospectively randomized into conventional wire closure (group C) or rigid fixation using sternal plates (group R). Pain scores were determined at 6 AM using a numeric rating scale (0 no pain, 5 moderate pain, 10 worst possible pain). Narcotic pain medication requirement from day 1 to 5 was collected and converted into intravenous morphine equivalent. Results: Among the total of 26 patients, 11 patients were in Group R (10 male and 1 female, age 67 ± 8.0) and 15 patients were in Group C (13 male and 2 female, age 66 ± 9.9). Preoperative risk factors and procedure were identical between the two groups. Pain scores were not significantly different between 2 groups. Narcotic requirement was smaller in group R (15.7 mg intravenous morphine equivalent in group R in day 1vs 18.4 mg intravenous morphine equivalent in day 1 in group C in day 1, 13.1 mg vs 12.5 mg in day 2, 9.4 mg vs 10.5 mg in day 3, 6.9 mg vs 7.7 mg in day 4, and 6.2 mg vs 6.9 mg in day 5) than group C. Total iv narcotic given over 5 days was 24 ± 41 mg in group R and 34 mg ± 54 mg in group C (p=0.60). Conclusion: Randomized data rom this ongoing study showed a trend of fewer narcotic requirement especially intravenous narcotics in group R than in group C. Implications: Rigid fixation may potentially improve immediate sternal pain after open heart surgery. Less narcotic requirement potentially facilitate early return to the daily activity

Mechanistic target of rapamycin complex 1 signaling regulates cell proliferation, cell survival, and differentiation in regenerating zebrafish fins

[Background]:The mechanistic target of rapamycin complex1 (mTORC1) signaling pathway has been implicated in functions of multicellular processes, including cell growth and metabolism. Although recent reports showed that many signaling pathways, including Activin, Bmp, Fgf, sonic hedgehog, Insulin-like growth factor (IGF), Notch, retinoic acid, and Wnt, are implicated in non-mammalian vertebrate regeneration, also known as epimorphic regeneration, mTORC1 function remains unknown. [Results]:To investigate the role of mTORC1 signaling pathway in zebrafish caudal fin, we examined the activation and function of mTORC1 signaling using an antibody against phosphorylated S6 kinase and a specific inhibitor, rapamycin. mTORC1 signaling is activated in proliferative cells of intra-ray and wound epidermal cells before blastema formation, as well as in proliferative blastema cells, wound epidermal cells, and osteoblasts during regenerative outgrowth. Before blastema formation, proliferation of intra-ray and wound epidermal cells is suppressed, but cell death is not affected by mTORC1 signaling inhibition with rapamycin. Moreover, rapamycin treatment inhibits blastema and wound epidermal cell proliferation and survival during blastema formation and regenerative outgrowth, as well as osteoblast proliferation and differentiation during regenerative outgrowth. We further determined that mTORC1 signaling is regulated through IGF-1 receptor/phosphatidylinositol-3 kinase and Wnt pathways during fin regeneration. [Conclusion]:Taken together, our findings reveal that mTORC1 signaling regulates proliferation, survival, and differentiation of intra-ray cells, wound epidermis, blastema cells, and/or osteoblasts in various fin regeneration stages downstream of IGF and Wnt signaling pathways.This study was supported by grants from Grant-in-Aid for Scientific Research from the JSPS (KAKENHI 23616002) to Y.K., and from Hiroshima University Alumni Association Research Grant & Hiroshima University Support Foundation Research and Grant-in-Aid for Scientific Research from the JSPS (KAKENHI 26 · 6771) to K.H

Thickened ascending aortic wall mimicking intramural hematoma.

A 45-year-old Hispanic woman presented with a 3-day history of ‘‘burning’’ chest pain. A computed tomo- graphic angiogram of the chest revealed the ascending aorta had a maximum diameter of 40 mm with marked thickening of the aortic wall (Figure 1), which we con- cluded was an intramural hematoma. On entering the pericardium, a milky-white plaque-like area on the ascending aorta was encountered (Figure 2). The ascending aorta was firm to palpation. Intraoperative transesophageal echocardiography and epiaortic ultra- sound showed a hyperechoic aortic wall with no find- ings compatible with aortic dissection. The ascending aorta had an irregular surface contour, which was unli- kely to be a finding of aortic dissection (Figure 3A, arrow). The transverse arch, proximal innominate artery, and left carotid artery also showed thickened walls (Figures 3B and 3C). We decided not to replace the ascending aorta. Pathology of the surface of the ascending aorta revealed a chronic inflammatory infiltrate with lymphocytes and plasma cells, dense fibrosis, and granulation. Serological studies were inconclusive. The patient was started on steroid therapy for possible isolated aortitis or aortitis syndrome, and her symptoms subsided with a normalized erythrocyte sedimentation rate and C-reactive protein level. She was doing well with a stable chest radiograph 10 months after the surgery