Interprofessional education in medical schools in Japan

Interprofessional education (IPE) for medical students is becoming increasingly important, as reflected in the increasing number of medical schools adopting IPE. However, the current status of and barriers to pre-registration IPE implementation in Japanese medical schools remain unknown. The purpose of this study was to clarify the status and barriers of IPE implementation in medical schools in Japan. We conducted a curriculum survey from September to December 2016 of all 81 medical schools in Japan. We mailed the questionnaire and asked the schools’ undergraduate education staff to respond. The survey items were the IPE implementation status and barriers to program implementation. Sixty-four of the 81 schools responded (response rate 79.0%), of which 46 (71.9%) had implemented IPE, 42 (89.1%) as compulsory programs. Half of IPE programs were implemented in the first 2 years, while less than 10% were implemented in the latter years of medical programs. As part of the IPE programs, medical students collaborated with a wide range of professional student groups. The most common learning strategy was lectures. However, one-third of IPE programs used didactic lectures without interaction between multi-professional students. The most common perceived major barrier to implementing IPE was adjustment of the academic calendar and schedule (82.8%), followed by insufficient staff numbers (73.4%). Our findings indicate that IPE is being promoted in undergraduate education at medical schools in Japan. IPE programs differed according to the circumstances of each school. Barriers to IPE may be resolved by improving learning methods, introducing group discussions between multi-professional students in lectures or introducing IPE programs using team-based learning. In summary, we demonstrated the current status and barriers of IPE implementation in Japanese medical schools. Our findings will likely lead to the promotion of IPE programs in Japan

Outcome of Allogeneic Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia Patients with Central Nervous System Involvement

AbstractCentral nervous system (CNS) involvement in adult acute myeloid leukemia (AML) is rare and associated with poor outcomes. Therefore, CNS involvement in AML is an indicator for allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the impact of CNS involvement in AML on the outcome of allo-HSCT remains unclear. We performed a large-scale nationwide retrospective analysis to elucidate the outcomes of allo-HSCT on AML with CNS involvement (CNS+AML). Clinical data were collected from a registry database of the Japan Society for Hematopoietic Cell Transplantation. CNS involvement was defined as the infiltration of leukemia cells into the CNS or myeloid sarcoma in the CNS identified at any time from diagnosis to transplantation. One hundred fifty-seven patients with CNS+AML underwent allo-HSCT between 2006 and 2011. The estimated overall survival, cumulative incidence of relapse and nonrelapse mortality at 2 years for CNS+AML (51.2%, 30.2%, and 14.5%, respectively) were comparable with those for AML without CNS involvement (48.6%, 27.4%, and 22.0%, respectively). Univariate and multivariate analyses indicated that the development of chronic graft-versus-host disease, disease status, and cytogenetic risk category were independent prognostic factors for overall survival for CNS+AML. These results suggest that allo-HSCT may improve outcomes in patients with CNS+AML

Allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia with t(6;9)(p23;q34) dramatically improves the patient prognosis: A matched-pair analysis

Acute myeloid leukemia (AML) with t(6;9)(p23;q34) is well known to have a poor prognosis treated with chemotherapy and autotransplantation. The presence of this karyotype is an indicator for allogeneic hematopoietic stem cell transplantation (HSCT); however, the impact of t(6;9)(p23;q34) on the HSCT outcome remains unclear. We conducted a matched-pair analysis of de novo AML patients with and without t(6;9)(p23;q34) using data obtained from the Japanese HSCT data registry. A total of 57 patients with t(6;9)(p23;q34) received transplants between 1996 and 2007, and 171 of 2056 normal karyotype patients matched for age, disease status at HSCT and graft source were selected. The overall survival, disease-free survival, cumulative incidence of relapse and the non-relapse mortality in t(6;9)(p23;q34) patients were comparable to those for normal karyotype patients. A univariate analysis showed that t(6;9)(p23;q34) had no significant impact on the overall survival. These findings suggest that allogeneic HSCT may overcome the unfavorable impact of t(6;9)(p23;q34) as an independent prognostic factor. © 2012 Macmillan Publishers Limited All rights reserved

Prognostic factors for acute myeloid leukemia patients with t(6;9)(p23;q34) who underwent an allogeneic hematopoietic stem cell transplant

We have recently reported that the outcome of acute myeloid leukemia (AML) patients with t(6;9)(p23;q34) who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) was comparable to that of patients with a normal karyotype. We performed a further analysis regarding the prognostic factors for t(6;9)(p23;q34) AML patients who underwent a HSCT. Seven pediatric patients and 57 adult patients, transplanted between 1996 and 2007, were assessed in this study. The overall survival (OS) of the pediatric patients tended to be better than the OS of the adults, although there were no statistically significant differences. The present study focused on the adult patients revealed that the disease status at HSCT was the sole prognostic factor affecting the OS identified in the univariate analysis. A multivariate analysis showed that the disease status at HSCT and M2 in the FAB classification were extracted as the significant variables affecting the OS. The patients who were not in remission at HSCT and had non-FAB-M2 showed a poorer outcome; 6 deaths in the 9 patients were due to a relapse of the AML. These findings suggest that novel therapeutic approaches might be needed for patients with these poor prognostic factors.発行後6か月より全文公開

Binding and uptake of H-ferritin are mediated by human transferrin receptor-1

Ferritin is a spherical molecule composed of 24 subunits of two types, ferritin H chain (FHC) and ferritin L chain (FLC). Ferritin stores iron within cells, but it also circulates and binds specifically and saturably to a variety of cell types. For most cell types, this binding can be mediated by ferritin composed only of FHC (HFt) but not by ferritin composed only of FLC (LFt), indicating that binding of ferritin to cells is mediated by FHC but not FLC. By using expression cloning, we identified human transferrin receptor-1 (TfR1) as an important receptor for HFt with little or no binding to LFt. In vitro, HFt can be precipitated by soluble TfR1, showing that this interaction is not dependent on other proteins. Binding of HFt to TfR1 is partially inhibited by diferric transferrin, but it is hindered little, if at all, by HFE. After binding of HFt to TfR1 on the cell surface, HFt enters both endosomes and lysosomes. TfR1 accounts for most, if not all, of the binding of HFt to mitogen-activated T and B cells, circulating reticulocytes, and all cell lines that we have studied. The demonstration that TfR1 can bind HFt as well as Tf raises the possibility that this dual receptor function may coordinate the processing and use of iron by these iron-binding molecules

Acute megakaryoblastic leukemia, unlike acute erythroid leukemia, predicts an unfavorable outcome after allogeneic HSCT

Acute erythroid leukemia (FAB-M6) and acute megakaryoblastic leukemia (FAB-M7) exhibit closely related properties in cells regarding morphology and the gene expression profile. Although allogeneic hematopoietic stem cell transplantation (allo-HSCT) is considered the mainstay of the treatment for both subtypes of leukemia due to their refractoriness to chemotherapy and high rates of relapse, it remains unclear whether allo-HSCT is curative in such cases due to their scarcity. We retrospectively examined the impact of allo-HSCT in 382 patients with M6 and 108 patients with M7 using nationwide HSCT data and found the overall survival (OS) and relapse rates of the M6 patients to be significantly better than those of the M7 patients after adjusting for confounding factors and statistically comparable with those of the patients with M0/M1/M2/M4/M5 disease. Consequently, the factors of age, gender, performance status, karyotype, disease status at HSCT and development of graft-vs.-host disease predicted the OS for the M6 patients, while the performance status and disease status at HSCT were predictive of the OS for the M7 patients. These findings substantiate the importance of distinguishing between M6 and M7 in the HSCT setting and suggest that unknown mechanisms influence the HSCT outcomes of these closely related subtypes of leukemia. © 2016 Elsevier Ltd.Embargo Period 12 month

シイクカ マレーグマ ニ オケル コウカテキ ナ サイショク エンリッチメント

マレーグマ（Helarctos malayanus）は，IUCNのレッドリストでは絶滅危惧II類（VU）に指定されている。絶滅危惧種の保全には，生息域内での生態・行動把握に加えて，動物園などでの生息域外保全も重要である。その際，飼育環境を自然生息地に近づけ，動物のもつ野生本来の行動を発現できるエンリッチメントが大切となってくる。しかし，飼育下マレーグマでエンリッチメントが行われている前例は世界でも少なく，国内では行われた報告がない。また過去にマレーグマにおいて効果的とされた採食エンリッチメントは広い放飼場を必要とする。そこで本研究は，飼育下マレーグマにおいて限られた空間で継続的な効果を望める採食エンリッチメントを考案することを目的とした。本研究は2つの実験を甲府市遊亀公園附属動物園（以下：甲府）と豊橋総合動植物公園（以下：豊橋）にて行った。実験1はブイ，丸太の2種類のエンリッチメントを設置し，それぞれの効果を検証した。実験2はブイを定期的に移動させることでエンリッチメントの効果持続を試みた。実験1より甲府で平均17.8%（最大27.1%），豊橋で平均24.3%（最大32.8%）の採食行動の増加と，甲府で平均42.0%（最大72.9%），豊橋で平均18.2%（最大25.7%）の常同行動の減少が確認できた。ブイ，丸太ともに効果が確認できたことに加え，野生下に類似した行動が発現し，エンリッチメントとして優れていると考えられる。しかし，丸太の効果は一時的なものであった。また，ブイを移動させることによって，エンリッチメントの効果を6ヶ月にわたる5回の調査期間全てで確認できた。さらに，給餌直後に限らず，給餌から最大7時間後の採食が確認できたことから，ブイの効果は1日を通してみられた。よって，ブイを定期的に移動させることで，限られた空間の中で継続的な効果のあるエンリッチメントを考案することができた。Sun bears (Helarctos malayanus), the world’s smallest bear, have been listed as vulnerable on the IUCN red list since 2017. For such endangered species, ex-situ conservation plays a vital role, and introducing enrichment in captive environment is important in prompting natural behaviors. However, only a few enrichment studies have been done on this species, and none in Japan. An enrichment proven to be effective for sun bears in a study done in Germany requires big outdoor enclosures that is difficult to recreate in most zoos. This study devises a new feeding enrichment for sun bears, with minimal space and long-lasting effects. Two experiments were done. In experiment 1, a log filled with honey and a buoy with a small hole were placed as a feeding enrichment, and the effects were measured. In experiment 2, to avoid habituation and to achieve prolonged effect, the buoy was moved after each 3-day observation period. The experiment was done in Yuki Park Zoo (Kofu), and Toyohashi Zoo and Botanical Park (Toyohashi). In experiment 1, foraging increased by an average of 17.8% in Kofu, and 24.3% in Toyohashi. Pacing declined by an average of 42.0% in Kofu, and 18.2% in Toyohashi. Both log and buoy were proven to be effective in increasing foraging activity and decreasing pacing. Moreover, in using the enrichment, behaviors such as digging and standing up using both hands to forage was seen, which resembles those seen in wild sun bears. However, the log’s effect was temporary. In experiment 2, by moving the buoy, decline of pacing and increase in foraging was seen over time, therefore, achieving prolonged effect. Foraging activity was also seen 7 hours after the enrichment was placed, indicating that this feeding enrichment’s effect lasts throughout the day. In conclusion, by moving the buoy regularly, this study developed an effective long-term feeding enrichment within the minimal space