Synthesis of Erythrochelin : A Hydroxamate-Type Siderophore from Saccharopolyspora erythraea

Erythrochelin, a hydroxamate-type siderophore produced by Saccharopolyspora erythraea, is synthesized for the first time. A key building block of erythrochelin containing the 2,5-diketopiperazine ring is prepared by intramolecular cyclization of the corresponding dipeptide precursor derived from two kinds of protected δ-N-hydroxy-L-ornithines. Consecutive condensation of the building block with protected D-serine and protected δ-N-hydroxy-D-ornithine, followed by deprotection, furnishes erythrochelin

The diagnosis of delayed expanding traumatic pseudoaneurysm of thoracic aorta caused by self-inflicted penetrating injury with crossbow bolt: A case report

Introduction and importance: Penetrating chest trauma caused by a crossbow bolt is very rare. Herein, we report a successfully treated patient who attempted suicide by directing a crossbow to the chest cavity and developed an expanding pseudoaneurysm of the thoracic aorta during eight-day follow up. Case presentation: A 51-year-old male was admitted to the emergency department after firing a crossbow bolt twice into his left chest. At admission, the patient was hemodynamically stable and maintaining oxygenation. The bolt had already been removed from the body. Contrast-enhanced computed tomography (CT) revealed a cavity pseudoaneurysm 2.5 mm in size in the aortic arch. Three-dimensional reconstruction of the CT demonstrated wound tracts showing probable damage by the bolt. The patient was admitted to the emergency department for careful observation and transferred to the psychiatric ward on day two. Follow-up contrast-enhanced CT on day eight demonstrated rapid expansion of the pseudoaneurysm from 2.5 mm to 4.0 mm in size. We performed thoracic endovascular aortic repair (TEVAR) on day 13. The patient was uneventfully discharged on the 20th hospital day. Clinical discussion: Emergency physicians should be aware that damage to the surrounding tissue may be accompanied by delayed expansion of an aortic pseudoaneurysm, even if the bolts do not cause direct aortic wall injury. Conclusion: This case suggests that understanding the injury mechanism, confirming the tract of the bolts, and carefully exploring traumatic pseudoaneurysm can lead to a less invasive operation due to early detection

横浜開港場の都市史研究

学位の種別: 課程博士審査委員会委員 : （主査）東京大学教授 伊藤 毅, 東京大学教授 藤井 恵介, 東京大学准教授 加藤 耕一, 横浜都市発展記念館主任調査研究員 青木 祐介, 飯田市歴史研究所所長 吉田 伸之University of Tokyo(東京大学

Right Hemiplegia Following Acute Carbon Monoxide Poisoning

Acute carbon monoxide (CO) poisoning remains a common cause of poison-related death and influences neurological function. An 83-year-old female was transferred to our emergency unit due to hypertension with dizziness, headache, and right hemiplegia. There was no radiographic evidence of ischemic stroke. The family members reported that the patient may have been exposed to CO by briquettes burned inside a closed room. High flow oxygen therapy was given for suspected CO intoxication and her symptoms quickly improved. Although we do not have clear evidence, we presume that hemiplegia in our patient was caused by CO intoxication, based on rapid recovery with oxygen therapy, carboxyhemoglobin (COHb) level elevation (3.0%), polycythemia, and neuroimaging. Despite the hematogenous effects of CO, paralysis appeared to be more severe on her right side than on her left side. MRI and blood tests helped to support CO as the suspected cause of her hemiplegia. This case reconfirms the importance of medical interviewing by medical practitioners, even in an emergency setting

A case of spontaneous mesenteric hematoma successfully diagnosed and treated with aggressive imaging

Introduction: Spontaneous mesenteric hematoma is an uncommon syndrome triggered by bleeding localized in the mesenteric vascular tree of a bowel segment for no apparent underlying reason. We herein report a surgical patient with an extremely rapidly growing spontaneous mesenteric hematoma that we successfully diagnosed using careful radiologic examination. Presentation of case: A 56-year-old old male presenting sudden onset lower abdominal pain was referred to our emergency department. At the time of admission, his physical examination revealed stable vital signs without radiological abnormality. On the following day, the patient suddenly presented hypotension, tachycardia, and increased abdominal pain. Contrast-enhanced computed tomography examination showed a mass with both high- and low-density areas with a 130 mm maximum diameter bordering the transverse colon. Since interventional radiologists were not available, we decided to perform emergency exploratory laparotomy. On laparotomy, a 13 × 8 cm hematoma was found in the mesentery of the transverse colon. As bleeding was noted from the branches of the middle colic artery and gastrocolic artery, these responsible vessels were ligated. The patient was finally given the diagnosis of spontaneous mesenteric hematoma. Discussion and conclusion: The present case, initially diagnosed as enterocolitis, suddenly manifested hypovolemic shock. Close monitoring for any signs of further deterioration, as well as aggressive imaging diagnosis, enabled us to avoid delays in treatment. Early diagnosis and treatment of mesenteric hematomas are essential to prevent them from rupturing and triggering life-threatening adverse events

Long-term, patient-centered, frailty-based outcomes of older critical illness survivors from the emergency department: a post hoc analysis of the LIFE Study

Background Evidence indicates frailty before intensive care unit (ICU) admission leads to poor outcomes. However, it is unclear whether quality of life (QOL) and activities of daily living (ADL) for survivors of critical illness admitted to the ICU via the emergency department remain consistent or deteriorate in the long-term compared to baseline. This study aimed to evaluate long-term QOL/ADL outcomes in these patients, categorized by the presence or absence of frailty according to Clinical Frailty Scale (CFS) score, as well as explore factors that influence these outcomes. Methods This was a post-hoc analysis of a prospective, multicenter, observational study conducted across Japan. It included survivors aged 65 years or older who were admitted to the ICU through the emergency department. Based on CFS scores, participants were categorized into either the not frail group or the frail group, using a threshold CFS score of Results Of 514 candidates, 390 participants responded to the EQ-5D-5L questionnaire, while 237 responded to the Barthel Index. At six months post-admission, mean EQ-5D-5L values declined in both the not frail and frail groups (0.80 to 0.73, p = 0.003 and 0.58 to 0.50, p = 0.002, respectively); Barthel Index scores also declined in both groups (98 to 83, p  Conclusions Regardless of frailty, older ICU survivors from the emergency department were more likely to experience reduced QOL and ADL six months after ICU admission compared to baseline

The Impact of Medical Students Teaching Basic Life Support to Laypersons

Basic life support (BLS) courses for laypersons, including cardiopulmonary resuscitation (CPR) training, is known to improve outcomes of out-of-hospital cardiac events. We asked medical students to provide BLS training for laypersons as a part of their emergency medicine education and evaluated the effects of training on the BLS skills of laypersons. We also used a questionnaire to determine whether the medical students who provided the BLS training were themselves more confident and motivated to perform BLS compared to students who did not provide BLS training. The proportions of laypersons who reported confidence in checking for a response, performing chest compressions, and automated external defibrillator (AED) use were significantly increased after the BLS training. The proportions of medical students who reported increased confidence/motivation in terms of understanding BLS, checking for a response, chest compression, use of AED, and willingness to perform BLS were significantly greater among medical students who provided BLS instructions compared to those who did not. BLS instruction by medical students was associated with an improvement in laypersons’ CPR accuracy and confidence in responding to cardiac arrest. The results indicate that medical students could gain understanding, confidence, and motivation in regard to their BLS skills by teaching BLS to laypersons

Rapidly evolving ultrafine and fine mode biomass smoke physical properties: Comparing laboratory and field results

Combining field and laboratory results, we present biomass smoke physical properties. We report sub-0.56 µm diameter (Dp) particle sizing (fast mobility particle sizer, FMPS) plus light absorption and scattering at 870nm (photoacoustic extinctiometer). For Dp\u3c200 \u3enm, the FMPS characterized sizing within ±20% compared to standards. As compared to the traditional scanning mobility particle sizer, the FMPS responded most accurately to single-mode polydispersions with mean Dp\u3c200 \u3enm, which characterized the smoke sampled here. Smoke was measured from laboratory fresh emissions (seconds to hours old), the High Park Fire (hours to\u3c1 \u3eday), and from regional biomass burning (several days). During a High Park Fire episode, light extinction rapidly reached a maximum of σep = 569 ± 21Mm-1 (10 min) with aerosol single scattering albedo peaking at ω= 0.955 ± 0.004. Concurrently, number concentration and size peaked with maximum Dp = 126nm and a unimodal distribution with σg = 1.5. Long-range transported smoke was substantially diluted (Ntot factor of 7 lower) and shifted larger (maximum Dp = 143) and wider (σg = 2.2). We compared ambient data to laboratory burns with representative western U.S. forest fuels (coniferous species Ponderosa pine and Alaska black spruce). Smoldering pine produced an aerosol dominated by larger, more strongly light scattering particles (Dp\u3e100 nm), while flaming combustion produced very high number concentrations of smaller (Dp ~ 50 nm) absorbing particles. Due to smoldering and particle growth processes, Dp approached 100nm within 3 h after emission. Increased particle cross-sectional area and Mie scattering efficiency shifted the relative importance of light absorption (flaming maximum) and light scattering (smoldering maximum), increasing ω over time. Measurements showed a consistent picture of smoke properties from emission to aging

Randomised, multicentre prospective trial of transarterial chemoembolisation (TACE) plus sorafenib as compared with TACE alone in patients with hepatocellular carcinoma: TACTICS trial.

OBJECTIVE:This trial compared the efficacy and safety of transarterial chemoembolisation (TACE) plus sorafenib with TACE alone using a newly established TACE-specific endpoint and pre-treatment of sorafenib before initial TACE. DESIGN:Patients with unresectable hepatocellular carcinoma (HCC) were randomised to TACE plus sorafenib (n=80) or TACE alone (n=76). Patients in the combination group received sorafenib 400 mg once daily for 2-3 weeks before TACE, followed by 800 mg once daily during on-demand conventional TACE sessions until time to untreatable (unTACEable) progression (TTUP), defined as untreatable tumour progression, transient deterioration to Child-Pugh C or appearance of vascular invasion/extrahepatic spread. Co-primary endpoints were progression-free survival (PFS), which is not a conventional one but defined as TTUP, or time to any cause of death plus overall survival (OS). Multiplicity was adjusted by gatekeeping hierarchical testing. RESULTS:Median PFS was significantly longer in the TACE plus sorafenib than in the TACE alone group (25.2 vs 13.5 months; p=0.006). OS was not analysed because only 73.6% of OS events were reached. Median TTUP (26.7 vs 20.6 months; p=0.02) was also significantly longer in the TACE plus sorafenib group. OS at 1 year and 2 years in TACE plus sorafenib group and TACE alone group were 96.2% and 82.7% and 77.2% and 64.6%, respectively. There were no unexpected toxicities. CONCLUSION:TACE plus sorafenib significantly improved PFS over TACE alone in patients with unresectable HCC. Adverse events were consistent with those of previous TACE combination trials. TRIAL REGISTRATION NUMBER:NCT01217034

MicroRNA-140 mediates RB tumor suppressor function to control stem cell-like activity through interleukin-6

We established an in vitro cell culture system to determine novel activities of the retinoblastoma (Rb) protein during tumor progression. Rb depletion in p53-null mouse-derived soft tissue sarcoma cells induced a spherogenic phenotype. Cells retrieved from Rb-depleted spheres exhibited slower proliferation and less efficient BrdU incorporation, however, much higher spherogenic activity and aggressive behavior. We discovered six miRNAs, including mmu-miR-18a, -25, -29b, -140, -337, and -1839, whose expression levels correlated tightly with the Rb status and spherogenic activity. Among these, mmu-miR-140 appeared to be positively controlled by Rb and to antagonize the effect of Rb depletion on spherogenesis and tumorigenesis. Furthermore, among genes potentially targeted by mmu-miR-140, Il-6 was upregulated by Rb depletion and downregulated by mmu-mir-140 overexpression. Altogether, we demonstrate the possibility that mmu-mir-140 mediates the Rb function to downregulate Il-6 by targeting its 3\u27-untranslated region. Finally, we detected the same relationship among RB, hsa-miR-140 and IL-6 in a human breast cancer cell line MCF-7. Because IL-6 is a critical modulator of malignant features of cancer cells and the RB pathway is impaired in the majority of cancers, hsa-miR-140 might be a promising therapeutic tool that disrupts linkage between tumor suppressor inactivation and pro-inflammatory cytokine response.Supplementary Table1 and Supplementary Table2: We offer the table data with an Excel fil