HLA loci predisposing to immune TTP in Japanese: potential role of the shared ADAMTS13 peptide bound to different HLA-DR.

Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare autoimmune disorder caused by neutralizing anti-ADAMTS13 autoantibodies. In white individuals, HLA allele DRB1*11 is a predisposing factor for iTTP, whereas DRB1*04 is a protective factor. However, the role of HLA in Asians is unclear. In this study, we analyzed 10 HLA loci using next-generation sequencing in 52 Japanese patients with iTTP, and the allele frequency in the iTTP group was compared with that in a Japanese control group. We identified the following HLA alleles as predisposing factors for iTTP in the Japanese population: DRB1*08:03 (odds ratio [OR], 3.06; corrected P [Pc] = .005), DRB3/4/5*blank (OR, 2.3; Pc = .007), DQA1*01:03 (OR, 2.25; Pc = .006), and DQB1*06:01 (OR,: 2.41; Pc = .003). The estimated haplotype consisting of these 4 alleles was significantly more frequent in the iTTP group than in the control group (30.8% vs 6.0%; Pc < .001). DRB1*15:01 and DRB5*01:01 were weak protective factors for iTTP (OR, 0.23; Pc = .076; and OR, 0.23, Pc = .034, respectively). On the other hand, DRB1*11 and DRB1*04 were not associated with iTTP in the Japanese. These findings indicated that predisposing and protective factors for iTTP differ between Japanese and white individuals. HLA-DR molecules encoded by DRB1*08:03 and DRB1*11:01 have different peptide-binding motifs, but interestingly, bound to the shared ADAMTS13 peptide in an in silico prediction model.

Pathological features of inflammatory myopathy as a manifestation of chronic graft-versus-host disease after allogeneic bone marrow transplantation.

Chronic graft-versus-host disease (cGVHD) is the most important complication resulting in the death of bone marrow transplantation (BMT) survivors. It is also a relatively rare cause of inflammatory myopathy (IM). We report the case of a 46-year-old woman who developed severe cGVHD-related IM after BMT for myelodysplastic syndrome. She presented with severe muscle pain and weakness with cGVHD-related symptoms in other organs. Myopathological analysis showed moderate cell infiltration with remarkable necrotic and regenerative fibers. Sarcoplasm and capillaries expressed C5b9 and myxovirus resistance protein 1. Non-necrotic fibers in perifascicular regions expressed MHC-II. Steroid therapy did not sufficiently control cGVHD-related IM, and the patient was concurrently treated with an immunosuppressant. Our findings show that IM is a key manifestation of cGVHD and that the expression of interferon-inducible proteins in muscle pathology is useful for identifying cGVHD-related IM.

Arthroscopic handlebar technique for the treatment of posterior malleolar fractures.

Treating posterior malleolar fractures of the ankle remains a challenge. The arthroscopic handlebar technique is our novel surgical method used for reduction and fixation of posterior malleolar fractures and involves the restoration of posterior malleolar fractures under anterior arthroscopic guidance and the use of Kirschner wires that penetrates the fractured posterior malleolus. Arthroscopy enables visualization of the intra-articular fracture of the posterior malleolus, and a handlebar reduction bar is used to control the fractured posterior malleolus. The arthroscopic handlebar technique is a promising procedure for reduction and internal fixation of the posterior malleolar fractures.

[Development of thrombocytopenic purpura following BNT162b2 mRNA COVID-19 vaccination].

Because the coronavirus disease 2019 (COVID-19) pandemic is still rampant, vaccination is being promoted worldwide. However, the safety of various COVID-19 vaccines remains poorly understood. We herein report the case of a 37-year-old woman who experienced thrombocytopenia following BNT162b2 mRNA COVID-19 vaccination. The patient presented with purpura on the extremities 10 days after the first vaccination. She had marked thrombocytopenia and no thrombosis. Thrombocytopenia resolved spontaneously. Given the possibility of occurrence of post-vaccination thrombocytopenia, vaccinated persons should be instructed to consult a medical institution if they experience bleeding symptoms.

GATA2 hypomorphism induces chronic myelomonocytic leukemia in mice.

The transcription factor GATA2 regulates normal hematopoiesis, particularly in- stem cell maintenance and myeloid differentiation. Various heteroallelic GATA2 gene mutations are associated with a variety of hematological neoplasms, including myelodysplastic syndromes and leukemias. Here, we report that impaired GATA2 expression induces myelodysplastic and myeloproliferative neoplasm development in elderly animals, and this neoplasm resembles chronic myelomonocytic leukemia in humans. GATA2 hypomorphic mutant (G2f GN / fGN ) mice that were generated by the germline insertion of a neocassette into the Gata2 gene locus avoided the early embryonic lethality observed in Gata2-null mice. However, adult G2f GN / fGN mice suffered from exacerbated leukocytosis concomitant with progressive anemia and thrombocytopenia and eventually developed massive granulomonocytosis accompanied by trilineage dysplasia. The reconstitution activity of G2f GN / fGN mouse stem cells was impaired. Furthermore, G2f GN / fGN progenitors showed myeloid lineage-biased proliferation and differentiation. Myeloid progenitor accumulation started at a younger age in G2f GN / fGN mice and appeared to worsen with age. G2f GN / fGN mice showed increased expression of transcripts encoding cytokine receptors, such as macrophage colony-stimulating factor receptor and interleukin-6 receptor, in granulocyte-monocyte progenitors. This increased expression could be correlated with the hypersensitive granulomonocytic proliferation reaction when the mice were exposed to lipopolysaccharide. Taken together, these observations indicate that GATA2 hypomorphism leads to a hyperreactive defense response to infections, and this reaction is attributed to a unique intrinsic cell defect in the regulation of myeloid expansion that increases the risk of hematological neoplasm transformation.

[Development of disseminated cryptococcosis during chemotherapy for plasmacytoma].

A 71-year-old male developed plasmacytoma on September 2015. He received radiotherapy, followed by posterior spinal fusion, at Th5 and L3 and was subsequently administered lenalidomide plus dexamethasone (Ld) from January 2016. After the 9th course of Ld, the patient complained of epigastric discomfort and papules on the face. FDG-PET showed duodenum 3rd potion and indicated nodular lesions with high glucose uptake on the lower lobe of the right lung and third portion of the duodenum. Biopsy of the skin, duodenum, and lung revealed Grocott's stain positive circular bodies, and the patient was subsequently diagnosed with disseminated cryptococcosis. Although disseminated cryptococcosis often causes encephalomeningitis, gastrointestinal involvement is rarely reported. The underlying conditions of disseminated cryptococcosis include AIDS, hematological malignancies, and steroid and immunosuppressant use. The sites of infections are the esophagus, stomach, small intestine, and colon. Disseminated cryptococcosis is diagnosed by abdominal pain, bloody stool, and gastrointestinal perforation. However, disseminated cryptococcosis may be asymptomatic; therefore, it is imperative that there is no delay in its diagnosis.

Induction of erythropoietin gene expression in epithelial cells by chemicals identified in GATA inhibitor screenings.

Erythropoietin (EPO) is a hormone that promotes proliferation, differentiation and survival of erythroid progenitors. EPO gene expression is regulated in a tissue-specific and hypoxia-inducible manner and is mainly restricted to renal EPO-producing cells after birth. Chronic kidney disease (CKD) confers high risk for renal anemia due to lower EPO production from injured kidneys. In transgenic reporter lines of mice, disruption of a GATA-binding motif within the Epo gene promoter-proximal region restores constitutive reporter expression in epithelial cells. Here, mitoxantrone and its analogues, identified as GATA factor inhibitors through high-throughput chemical library screenings, markedly induce EPO/Epo gene expression in epithelium-derived cell lines and mice regardless of oxygen levels. In contrast, mitoxantrone interferes with hypoxia-induced EPO gene expression in Hep3B cells. Cryptic promoters are created for the EPO/Epo gene expression in epithelial cells upon mitoxantrone treatment, and consequently, unique 5'-untranslated regions are generated. The mitoxantrone-induced aberrant transcripts contribute to the reporter protein production in epithelial cells that carry the reporter gene in the proper reading frame of mouse Epo gene. Thus, EPO production in uninjured adult epithelial cells may be a therapeutic approach for renal anemia in patients with CKD.

Short-term efficacy and safety of hyaluronic acid injection for plantar fasciopathy.

PURPOSE: Plantar fasciopathy is the most common cause of plantar heel pain and is considered to be a type of enthesopathy. The short-term efficacy, safety, and dose-response relationship of high-molecular-weight hyaluronic acid (HA) was investigated in patients with plantar fasciopathy. METHODS: In this multicenter, prospective, randomized, double-blind, placebo-controlled trial, 168 patients with persistent pain from plantar fasciopathy for more than 12 weeks were randomly assigned to receive 2.5 mL of 1% HA (H-HA), 0.8 mL of 1% HA (L-HA), or 2.5 mL of 0.01% HA (control group) once a week for 5 weeks. The primary endpoint was improvement in visual analogue scale (VAS) score for pain from baseline to week 5. RESULTS: The VAS scores (least squares mean ± standard error) in each group decreased gradually after the start of treatment, a change of -3.3 ± 0.3 cm for the H-HA group, -2.6 ± 0.3 cm for the L-HA group, and -2.4 ± 0.3 cm for the control group, with the H-HA group improving significantly more than the control group (P = 0.029). No serious adverse events were reported. There was no difference between the groups in the incidence rates of adverse drug reactions. CONCLUSION: The administration of five injections of high-molecular-weight HA is an effective treatment with no serious adverse drug reactions and is a conservative treatment option for plantar fasciopathy. This treatment contributed to alleviation of pain in patients with plantar fasciopathy and improvement in their activities of daily living. LEVEL OF EVIDENCE: I.

Incidence and the risk factors of spinal deformity in adult patient after spinal cord injury: a single center cohort study.

STUDY DESIGN: A retrospective consecutive case series of adult spinal cord injuries (SCIs) patients. OBJECTIVE: To assess the incidence and risk factors of spinal deformity in a large sample of patients with SCIs. Post-traumatic spinal deformities are well-recognized sequelae of SCIs. Despite the devastating complications for SCI patients with trunk imbalance, the incidence, clinical outcomes, and independent risk factors of scoliosis after SCI remain controversial. MATERIALS AND METHODS: We assessed 214 consecutive adult compressive SCI patients who were hospitalized in our hospital. We compared patients who developed spinal deformities with those who did not. Univariate and multivariate analyses to determine the independent risk factors were performed. Age, gender, etiology, ASIA grade (American Spinal Injury Association) surgery, and other demographic data were analyzed to determine the risk factors for developing a spinal deformity. RESULTS: The average patient age was 58.3 years (20-86 years). The etiology was trauma (n = 158), ossification of ligament (n = 22), infectious (n = 17), and others. One hundred fifty-two patients had cervical spine involved, 62 had thoracic spine involved. 26 patients classified as ASIA A, 54 were ASIA B, 96 were ASIA C, and 42 were ASIA D 4. One hundred thirty-five patients had either decompression or decompression and fusion surgery. The incidence of spinal deformities was 21 % (44/214). The mean Cobb angle was 28.9 degrees (13-38°). ASIA grade and surgery predicted the occurrence of spinal deformity in both the univariate model (ASIA grade, OR: 1.59 [95 % CI: 1.04-2.44; P = 0.032]; Surgery, OR: 4.47 [95 % CI: 1.89-10.06; P = 0.0007]) and the multivariate model (ASIA grade, OR: 1.63 [95 % CI: 1.04-2.57; P = 0.033]; Surgery, OR: 4.59 [95 % CI: 1.91-11.04; P = 0.0006]), whereas surgery was the most important risk factor in the Cox model (HR: 3.50 [95 % CI: 1.56-7.88; P = 0.0025]). CONCLUSIONS: The SCI patients with high ASIA grades and those who had undergone surgery had a higher likelihood of developing a spinal deformity. Of these risk factors, surgery was the stronger risk factor.

Verification of the in vivo activity of three distinct cis-acting elements within the Gata1 gene promoter-proximal enhancer in mice.

The transcription factor GATA1 is essential for erythroid and megakaryocytic cell differentiation. Gata1 hematopoietic regulatory domain (G1HRD) has been shown to recapitulate endogenous Gata1 gene expression in transgenic mouse assays in vivo. G1HRD contains a promoter-proximal enhancer composed of a GATA-palindrome motif, four CP2-binding sites and two CACCC boxes. We prepared transgenic reporter mouse lines in which green fluorescent protein and ß-galactosidase expression are driven by wild-type G1HRD (as a positive control) and the G1HRD harboring mutations within these cis-acting elements (as the experimental conditions), respectively. Exploiting this transgenic dual reporter (TDR) assay, we show here that in definitive erythropoiesis, G1HRD activity was markedly affected by individual mutations in the GATA-palindrome motif and the CACCC boxes. Mutation of CP2-binding sites also moderately decreased G1HRD activity. The combined mutation of the CP2-binding sites and the GATA-palindrome motif resulted in complete loss of G1HRD activity. In contrast, in primitive erythroid cells, individual mutations of each element did not affect G1HRD activity; G1HRD activity was abolished only when these three mutations were combined. These results thus show that all three elements independently and cooperatively contribute to G1HRD activity in vivo in definitive erythropoiesis, although these are contributing redundantly to primitive erythropoiesis.

Mature erythrocyte membrane homeostasis is compromised by loss of the GATA1-FOG1 interaction.

GATA1 plays essential roles in erythroid gene expression. The N-terminal finger of GATA1 (GATA1-Nf) is important for association with FOG1. Substitution mutations in GATA1-Nf, such as GATA1(V205M) that diminish the GATA1-FOG1 association, have been identified in human thrombocytopenia and anemia cases. A mouse model of human thrombocytopenia has been established using a transgenic complementation rescue approach; GATA1-deficient mice were successfully rescued from embryonic lethality by excess expression of GATA1(V205G), but rescued adult mice suffered from severe thrombocytopenia. In this study, we examined GATA1-deficient mice rescued with GATA1(V205G) at a comparable level to endogenous GATA1. Mice rescued with this level of GATA1(V205G) rarely survive to adulthood. Rescued newborns suffered from severe anemia and jaundice accompanied with anisocytosis and spherocytosis. Expression of Slc4a1, Spna1, and Aqp1 genes (encoding the membrane proteins band-3, α-spectrin, and aquaporin-1, respectively) were strikingly diminished, whereas expression of other canonical GATA1-target genes, such as Alas2, were little affected. Lack of these membrane proteins provoked perturbation of membrane skeleton. Importantly, the red cells exhibited increased reactive oxygen species accumulation. These results thus demonstrate that the loss of the GATA1-FOG1 interaction causes a unique combination of membrane protein deficiency and disturbs the function of GATA1 in maintaining erythroid homeostasis.

Developing a national food defense guideline based on a vulnerability assessment of intentional food contamination in Japanese food factories using the CARVER+Shock vulnerability assessment tool.

The awareness of food terrorism has increased following the September 11, 2001 terrorist attacks in New York City, United States, and many measures and policies dealing with this issue have been established worldwide. Suspected deliberate food-poisoning crimes have occurred in Japan, although they are not regarded as acts of food terrorism. One area of concern is that the small- to medium-sized companies that dominate Japan's food industry are extremely vulnerable to deliberate food poisoning. We conducted a literature research on food defense measures undertaken by the World Health Organization and in the United States and Europe. Using the Carver+Shock vulnerability assessment tool, eight food factories and related facilities in Japan were evaluated and we found the level of awareness of food defense to be low and the measures inappropriate. On the basis of this evaluation, we developed a set of guidelines that Japanese food companies can use to help develop their food defense strategies and to serve as a reference in considering specific measures.

Tentative food defense guidelines for food producers and processors in Japan.

OBJECTIVES: With increasing global interest in intentional food contamination, expert meetings have been held by the G8, while the U.S. government has proposed policies for preventing food terrorism and intentional contamination. However, Japan has no food defense policy, and some food companies are concerned about an impending terrorism and contamination crisis. METHODS: We developed a Food Defense Checklist for Food Producers and Processors and published the details on the website. We also developed tentative Food Defense Guidelines for Food Producers and Processors on the basis of the checklist. In this study, we tested the usability of the guidelines through a hearing survey regarding food plants. We also compared the checklist with the implementation manual for the approval system of Comprehensive Sanitation Management and Production Process (the Japanese equivalent of the HACCP). RESULTS: We organized the comments gleaned from the hearing survey and provided a detailed explanation of the guidelines. As the HACCP has been adopted by Japanese food companies, we included both precautionary measures and the HACCP perspective in the explanation regarding the rapid dissemination of information. CONCLUSION: The guidelines are useful for Japanese food companies, and it is important to disseminate knowledge on this topic and implement food defense measures.

Unveiling the natural history of paralysis in metastatic cervical spinal tumor: An experimental study.

Introduction: Despite the relatively low prevalence of metastatic cervical spinal tumor, these entities give rise to more profound complications than thoracic and lumbar spinal tumor. However, it is regrettable that experimental investigation has thus far shown a dearth of attention to metastatic cervical spinal tumor. Research question: What is the conceptualization and realization of quadriparesis resulting from metastatic cervical spinal tumor? Material and methods: Using Fischer 344 rats as the experimental cohort, this study orchestrated the engraftment of tumor cells procured from the 13762 MAT B III cell line (RRID: CVCL_3475), which represents mammary adenocarcinoma. These cells were engrafted into the vertebrae of the cervical spine. A comprehensive inquiry encompassing behavioral assessments, histological evaluations, and microangiographic analyses conducted after the aforementioned cellular transplantation was subsequently pursued. Results: The incidence of cervical paralysis was 61.1%. Notably, the evolution of paralysis was unfurled by two distinctive temporal phases within its natural history. A meticulous histological examination facilitated delineation of the tumor's posterior expansion within the spinal canal. Simultaneously, the tumor exhibited anterior and lateral encroachment on the spinal cord, inducing compression from all sides. Augmented by microangiographic investigations, conspicuous attenuation of stained blood vessels within the affected anterior horn and funiculus of the spinal cord was observed. Discussion and conclusion: The pathological advancement of paralysis stemming from metastatic cervical spinal tumor is now apprehended to unfurl through a biphasic phase. The initial phase is characterized by gradual unfurling spanning several days, juxtaposed against the second phase marked by swift and accelerated progression.

The abundance of the short GATA1 isoform affects megakaryocyte differentiation and leukemic predisposition in mice.

Transcription factor GATA1 controls the delicate balance between proliferation, differentiation and apoptosis in both the erythroid and megakaryocytic lineages. In addition to full-length GATA1, there is an GATA1 isoform, GATA1s, that lacks the amino-terminal transactivation domain. Somatic GATA1 mutations that lead to the exclusive production of GATA1s appear to be necessary and sufficient for the development of a preleukemic condition called transient myeloproliferative disorder (TMD) in Down syndrome newborns. Subsequent clonal evolution among latent TMD blasts leads to the development of acute megakaryoblastic leukemia (AMKL). We originally established transgenic mice that express only GATA1s, which exhibit hyperproliferation of immature megakaryocytes, thus mimicking human TMD; however, these mice never developed AMKL. Here, we report that transgenic mice expressing moderate levels of GATA1s, i.e., roughly comparable levels to endogenous GATA1, were prone to develop AMKL in young adults. However, when GATA1s is expressed at levels significantly exceeding that of endogenous GATA1, the development of leukemia was restrained in a dose dependent manner. If the transgenic increase of GATA1s in progenitors remains small, GATA1s supports the terminal maturation of megakaryocyte progenitors insufficiently, and consequently the progenitors persisted, leading to an increased probability for acquisition of additional genetic modifications. In contrast, more abundant GATA1s expression compensates for this maturation block, enabling megakaryocytic progenitors to fully differentiate. This study provides evidence for the clinical observation that the abundance of GATA1s correlates well with the progression to AMKL in Down syndrome.

Whole blood transcriptome analysis for age- and gender-specific gene expression profiling in Japanese individuals.

Whole blood transcriptome analysis is a valuable approachin medical research, primarily due to the ease of sample collection and the richness of the information obtained. Since the expression profile of individual genes in the analysis is influenced by medical traits and demographic attributes such as age and gender, there has been a growing demand for a comprehensive database for blood transcriptome analysis. Here, we performed whole blood RNA sequencing (RNA-seq) analysis on 576 participants stratified by age (20-30s and 60-70s) and gender from cohorts of the Tohoku Medical Megabank (TMM). A part of female segment included pregnant women. We did not exclude the globin gene family in our RNA-seq study, which enabled us to identify instances of hereditary persistence of fetal hemoglobin based on the HBG1 and HBG2 expression information. Comparing stratified populations allowed us to identify groups of genes associated with age-related changes and gender differences. We also found that the immune response status, particularly measured by neutrophil-to-lymphocyte ratio (NLR), strongly influences the diversity of individual gene expression profiles in whole blood transcriptome analysis. This stratification has resulted in a data set that will be highly beneficial for future whole blood transcriptome analysis in the Japanese population.

Arthroscopic excision of separated ossicles of the lateral malleolus.

BACKGROUND: We have conducted a retrospective review of 19 patients for whom 20 separated ossicles of the lateral malleolus were excised arthroscopically. We examined the operating methods, findings, and overall results. METHODS: The patients' indications for this procedure were as follows. The main complaints were pain alone; ossicle sizes were small and ankle instability was minimal. There were 12 ankles of 12 males and eight ankles of seven females. The patients' average age was 17.6 years. A 2.7-mm, 30° arthroscope was inserted into the ankle joint through the anterolateral portal. Instruments were inserted through the accessory anterolateral portal, and ossicles were removed piece by piece. Talar tilt angles and anterior displacements were examined and compared before and after surgery by use of stress radiographs. Japanese Society for Surgery of the Foot (JSSF) ankle/hindfoot scales were assessed pre and postoperatively. RESULTS: All patients recovered their original levels of activity. The mean talar tilt angle changed from 6.1° ± 2.4° preoperatively to 6.0° ± 1.8° postoperatively (p = 0.93), and the mean anterior displacement changed from 5.9 ± 1.7 mm preoperatively to 6.1 ± 2.0 mm postoperatively (p = 0.42). Average JSSF ankle/hindfoot scale improved from 77.6 ± 2.6 points preoperatively to 97.2 ± 5.2 points postoperatively (p < 0.01). CONCLUSIONS: Arthroscopic excision of separated ossicles of the lateral malleolus achieved good results with minimum incisions, and relatively early resumption of daily and sports activity was possible. However, when the ossicles were embedded within the fibers of the anterior talofibular ligament, it was impossible to avoid cutting of ligament fibers. To reduce the possibility of ligament dysfunction, we believe postoperative treatment should conform to the accepted method for treatment of acute ankle sprains.

Load distribution structure of rear bumper beam to enhance vehicle body energy absorption in rear-end collisions.

OBJECTIVE: This research focused on FMVSS301, which is required for higher energy absorption as a regulation for rear-end collisions. Since they are offset collisions, the deformation of the non-collision side frame, which does not directly contact the barrier, is less than on the collision side. The reason is that the rear bumper beam with curvature is deformed into a straight shape by the load from the barrier, resulting in an asymmetrical load distribution from the barrier that is biased toward the collision side. Therefore, the objective of this research was to construct a new bumper beam structure that reduces the difference in the load input to both frames and increases the energy absorption of the non-collision side frame. METHOD: The basic principle is to generate a counterforce against the lateral loads during transmitting the load from barrier to the frames. To achieve this, a bow-shaped rear bumper beam structure was devised. The rear bumper beam corresponds to the bow and the newly added connection plate to the string. The lateral load increase is suppressed and load distribution to the rear frame is maintained. RESULTS: The designed rear bumper beam and rear components equipped with the rear bumper beam were both prepared and evaluated by drop test. With testing of the rear bumper beam, it was demonstrated that the load in the lateral direction, which conventionally generates over 80 kN, could be canceled. Tests of the rear component demonstrated that load distribution to the rear frame could be maintained, and the energy absorption of the non-collision side frame could be enhanced by 35 times. The total energy absorption of the barrier and the two frames was demonstrated to increase 2.9 times. CONCLUSION: The bow-shaped rear bumper beam was designed to distribute the load evenly to the collision and non-collision side frames, and to deform both frames, thereby achieving a higher energy absorption of the entire vehicle body. This is expected to be applicable to electric vehicles and FCVs, which require more energy absorption with increased vehicle weight.

New load transfer structure to reduce body deformation in side collisions.

OBJECTIVE: In this research, body technology was established for side collisions with new IIHS MDB as a representative case. In the conventional body structure, most of the load received from the barrier is absorbed by bending deformation of the door beam and B-pillar, etc. For that reason, the body is subjected to large deformation before reaching the maximum load, and the deformation increases further when subjected to a high-energy collision. Therefore, the objective of this research is to create a structure that increases the load from the initiation of impact and suppresses the deformation of the car body. METHOD: An arched door beam was developed to reduce the bending moment by the axial load in the longitudinal direction generated during the deformation and to increase the load in the lateral direction. A principle equation was developed that uses the shape of the door beam as a variable. A prototype of the arched door beam was fabricated, and its performance was evaluated by an impactor test. A full-car simulation was conducted using a mass-produced sedan as a base, to which the arched door beam was added to verify the performance of the complete vehicle. RESULTS: The results of the impactor tests were evaluated using the load gradient, which was defined as the generated load divided by the amount of deformation. Compared to conventional straight door beams, the load gradient was 7.1 times higher. Full-car simulation results showed that for a gasoline-powered vehicle body weight, the body load gradient of the proposed structure was 4.7 times higher, and the body deformation adjacent to the dummy shoulder was reduced by 210 mm. Spine acceleration of the dummy was reduced by 56%. CONCLUSION: The body structure proposed in this research has the effect of increasing the load gradient and reducing body deformation and spine acceleration. It is expected to be applicable to EVs and FCVs, which require more energy absorption due to their increased vehicle weight.

Nrf2 alleviates spaceflight-induced immunosuppression and thrombotic microangiopathy in mice.

Spaceflight-related stresses impact health via various body systems, including the haematopoietic and immune systems, with effects ranging from moderate alterations of homoeostasis to serious illness. Oxidative stress appears to be involved in these changes, and the transcription factor Nrf2, which regulates expression of a set of cytoprotective and antioxidative stress response genes, has been implicated in the response to spaceflight-induced stresses. Here, we show through analyses of mice from the MHU-3 project, in which Nrf2-knockout mice travelled in space for 31 days, that mice lacking Nrf2 suffer more seriously from spaceflight-induced immunosuppression than wild-type mice. We discovered that a one-month spaceflight-triggered the expression of tissue inflammatory marker genes in wild-type mice, an effect that was even more pronounced in the absence of Nrf2. Concomitant with induction of inflammatory conditions, the consumption of coagulation-fibrinolytic factors and platelets was elevated by spaceflight and further accelerated by Nrf2 deficiency. These results highlight that Nrf2 mitigates spaceflight-induced inflammation, subsequent immunosuppression, and thrombotic microangiopathy. These observations reveal a new strategy to relieve health problems encountered during spaceflight.