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Curling is a target‐based team sport played in a cold environment. The type of stress curling players face during a curling match remains to be determined. In the present study, 16 Japanese curling players performed a practice curling match (six ends lasting 90 min), wherein the following variables were documented: core and skin temperatures, heart rate, thermal sensation and comfort, urine‐specific gravity, body fluid loss, salivary cortisol, α‐amylase activity, salivary secretory immunoglobulin A (SIgA), and fractionated exhaled nitric oxide (FeNO, a respiratory stress marker). Pre‐match resting core temperature was 37.24 ± 0.31°C, which increased up to 37.73 ± 0.41°C during the match (p < 0.001). Facial skin temperatures decreased after the match (all p ≤ 0.015), whereas finger skin temperatures remained unchanged (p ≥ 0.375). Thermal discomfort increased following the match but thermal sensation remained unchanged. Following the match, players lost 0.29 ± 0.15 L body fluid (sweat, respiratory evaporation, and urine), which was nearly compensated by fluid ingestion of 0.22 ± 0.13 L (p = 0.119). Nevertheless, urine‐specific gravity increased from 1.021 ± 0.010 to 1.024 ± 0.008 after the match (p = 0.012), with 31% and 50% players being dehydrated at pre‐ and post‐match, respectively. Salivary cortisol decreased (p < 0.001) after the match without changes in salivary SIgA, α‐amylase activity, and FeNO (all p ≥ 0.113). Therefore, during a curling match, the core temperature and thermal discomfort increase, whereas the face skin temperature decreases. Additionally, players may undergo dehydration before the match, which could be exacerbated after the match. [ABSTRACT FROM AUTHOR]

Purpose: Mammography is the only modality for breast cancer screening demonstrated to reduce the mortality rate. However, ultrasonographic screening is already being widely performed as opportunistic screening in Japan. The recall criteria for masses are very important as quality controls. The purpose of this study was to verify these criteria at multiple institutions. Methods: Screening was performed by five institutions in various regions in Japan. The total number of cases screened at all five institutions was 10,519. Results: The findings that could be concluded to be benign were a cystic pattern and three features of a solid pattern. The cystic pattern was noted in 6512 cases, typical fibroadenoma in 1483 cases, and typical complicated cyst in 70 cases. Only three of these 8065 cases were cancers, so the negative predictive value was 99.9%. The solid pattern with obvious malignant features, i.e., masses with an echogenic halo and/or interruption of the interface and masses with multiple echogenic foci, were noted in 33 cases. Twenty of the 33 cases were malignancy, resulting in a positive predictive value of 66.7%. Conclusion: Although some parts of the criteria should be considered further for verification and revision, the current recall criteria are mostly valid. [ABSTRACT FROM AUTHOR]

Fanconi anemia (FA) results from mutations in the genes necessary for DNA damage repair and often leads to progressive bone marrow failure. Although the exhaustion of the bone marrow leads to cytopenias in FA patients as they age, evidence from human FA and mouse model fetal livers suggests that hematopoietic defects originate in utero, which may lead to deficient seeding of the bone marrow. To address this possibility, we examined the consequences of loss of Fancd2 , a central component of the FA pathway. Examination of embryonic day 14.5 (E14.5) Fancd2 knockout (KO) fetal livers showed a decrease in total cellularity and specific declines in long-term and short-term hematopoietic stem cell (LT-HSC and ST-HSC, respectively) numbers. Fancd2 KO fetal liver cells display similar functional defects to Fancd2 adult bone marrow cells, including reduced colony-forming units, increased mitomycin C sensitivity, increased LT-HSC apoptosis, and heavily impaired competitive repopulation, implying that these defects are intrinsic to the fetal liver and are not dependent on the accumulation of DNA damage during aging. Telomere shortening, an aging-related mechanism proposed to contribute to HSC apoptosis and bone marrow failure in FA, was not observed in Fancd2 KO fetal livers. In summary, loss of Fancd2 yields significant defects to fetal liver hematopoiesis, particularly the HSC population, which mimics key phenotypes from adult Fancd2 KO bone marrow independently of aging-accrued DNA damage. [ABSTRACT FROM AUTHOR]

The crystal structures of a subunit of the formylglycinamide ribonucleotide amidotransferase, PurS, from Thermus thermophilus, Sulfolobus tokodaii and Methanocaldococcus jannaschii were determined and their structural characteristics were analyzed. For PurS from T. thermophilus, two structures were determined using two crystals that were grown in different conditions. The four structures in the dimeric form were almost identical to one another despite their relatively low sequence identities. This is also true for all PurS structures determined to date. A few residues were conserved among PurSs and these are located at the interaction site with PurL and PurQ, the other subunits of the formylglycinamide ribonucleotide amidotransferase. Molecular-dynamics simulations of the PurS dimer as well as a model of the complex of the PurS dimer, PurL and PurQ suggest that PurS plays some role in the catalysis of the enzyme by its bending motion. [ABSTRACT FROM AUTHOR]

Abstract: The pathogenesis of moyamoya disease remains unknown. Examination of diseases concurrent with moyamoya disease may offer a clue to clarify the pathogenesis. Coexistence of moyamoya disease, Graves’ disease, and diabetes mellitus is very rare. We present the first cases in the literature. A 38-year-old man with moyamoya disease and a 43-year-old woman with quasi-moyamoya disease, both concurrent with Graves’ disease and type 2 diabetes mellitus, are presented. Both patients underwent antithyroid therapy and revascularization. After normalization of thyroid hormones level and blood glucose level followed by revascularization, the symptoms of cerebral ischemia were improved. The common etiological factors of these diseases are discussed. Genetic and autoimmune factor appeared to be involved in the pathogenesis of the three diseases, which may suggest that these factors play important roles in the pathogenesis of moyamoya disease. Further studies are required to define the pathogenesis of moyamoya disease, especially in cases with comorbidities as in the present patients. [Copyright &y& Elsevier]

Phellinus linteus, a natural growing mushroom, has been known to exhibit anti-tumor, anti-inflammatory, anti-allergic and antioxidant effects. Aiming to exploit the neuroprotective effects of P. linteus, we evaluated its effects on infarct volume reduction in a rat model of focal cerebral ischemia. Male Sprague-Dawley rats were subjected to right middle cerebral artery occlusion. Filtrate of P. linteus broth culture (various doses), fractionated filtrate (based on molecular weight) or control medium was administered intraperitoneally to rats before or after ischemia induction. Rats were killed at 24 h after the stroke surgery. Cortical and caudoputaminal infarct volumes were determined separately using an image analysis program following staining with 2,3,5-triphenyltetrazolium chloride. Significant cortical infarct volume reductions were found in the pre-treatment groups (30 and 60minutes before onset of cerebral ischemia) compared with the control group, showing dose dependence. Posttreatment (30minutes after ischemic onset) also significantly reduced cortical infarct volume. Furthermore, the higher molecular weight (=12 000) fraction of the culture filtrate was more effective compared with the lower molecular weight fraction. The present findings suggest that P. linteus may be a new promising approach for the treatment of focal cerebral ischemia, with the additional benefit of a wide therapeutic time window since significant infarct volume reduction is obtained by administration even after the ischemic event. Our finding that the higher molecular weight fraction of the P. linteus culture filtrate demonstrated more prominent effect may provide a clue to identify the neuroprotective substances and mechanisms. [ABSTRACT FROM AUTHOR]

Background Current methods for the quantitative determination of glycogen in erythrocytes are unsatisfactory. Methods Erythrocytes were deproteinized with perchloric acid either after haemolysing by freezing and thawing twice or without freezing and thawing, and the glycogen content was determined by an enzymatic method. Results Freezing and thawing resulted in a significantly higher glycogen content, and the recovery of added glycogen using this method was nearly 100%. The mean erythrocyte glycogen content in healthy volunteers ( n =17) was 69·5μg/g haemoglobin, a value much higher than the previously reported values in healthy subjects. Conclusion Freezing and thawing improves the assay of erythrocyte glycogen. [ABSTRACT FROM AUTHOR]

Introduction Allo HCT is a curative option for many aggressive hematological malignancies that increase with age. HAPLO donors and UCB are alternative sources of hematopietic cells for patients lacking a matched sibling or unrelated donor. The choice between UCB and HAPLO HCT is challenging as there is no direct comparison between the two. Objectives The goal of this study is to compare outcomes of UCB vs HAPLO HCT in patients ≥ 60 years who received an allo-HCT at UMass Memorial Medical Center over the past 5 years. Methods We retrospectively analyzed data of all patients ≥ 60 years who underwent allo-HCT with either HAPLO or UCB between June 2013 – June 2018. Patient characteristics were collected from the electronic medical records. We assessed rates of neutrophil and platelet engraftment, length of hospitalization, rates of acute (a) and chronic (c) graft vs host disease (GVHD), relapse rates, as well as day 100 and 1 year nonrelapse mortality (NRM) and overall survival (OS) rates. Results Tables 1 & 2 summarize patient characteristics and HCT outcomes. 22 patients were identified from the database. All patients received RIC with Thiotepa/Fludarabine/Melphalan with the exception of 1 UCB patient who received Fludarabine/Cyclophosphamide. UCB patients received GVHD prophylaxis with tacrolimus/mycophenolate/antithymocyte globulin (ATG). HAPLO cohort received GVHD prophylaxis with post-transplant cyclophosphamide (PTCy) plus tacrolimus/sirolimus/ATG. Conclusion Despite the higher HCT-CI/age in the HAPLO group, its day-100 NRM rate was lower. Although day 100 OS was superior in HAPLO, the 1-year OS rate was similar in both cohorts. The use of PTCy in HAPLO GVHD prophylaxis may explain the higher relapse rate. Length of hospitalization is markedly shorter for HAPLO, which may translate into lower HCT cost. These results need to be validated in a prospective randomized trial. UCB and HAPLO HCT are both feasible in patients ≥ 60 years. The choice should rely on the urgency of HCT, available cell dose and the expertise of the HCT center. [ABSTRACT FROM AUTHOR]

Human bone marrow failure (BMF) syndromes result from the loss of hematopoietic stem and progenitor cells (HSPC), and this loss has been attributed to cell death; however, the cell death triggers, and mechanisms remain unknown. During BMF, tumor necrosis factor-α (TNFα) and interferon-γ (IFNγ) increase. These ligands are known to induce necroptosis, an inflammatory form of cell death mediated by RIPK1, RIPK3, and MLKL. We previously discovered that mice with a hematopoietic RIPK1 deficiency ( Ripk1 HEM KO ) exhibit inflammation, HSPC loss, and BMF, which is partially ameliorated by a RIPK3 deficiency; however, whether RIPK3 exerts its effects through its function in mediating necroptosis or other forms of cell death remains unclear. Here, we demonstrate that similar to a RIPK3 deficiency, an MLKL deficiency significantly extends survival and like Ripk3 deficiency partially restores hematopoiesis in Ripk1 HEM KO mice revealing that both necroptosis and apoptosis contribute to BMF in these mice. Using mouse models, we show that the nucleic acid sensor Z-DNA binding protein 1 (ZBP1) is up-regulated in mouse RIPK1-deficient bone marrow cells and that ZBP1's function in endogenous nucleic acid sensing is necessary for HSPC death and contributes to BMF. We also provide evidence that IFNγ mediates HSPC death in Ripk1 HEM KO mice, as ablation of IFNγ but not TNFα receptor signaling significantly extends survival of these mice. Together, these data suggest that RIPK1 maintains hematopoietic homeostasis by preventing ZBP1 activation and induction of HSPC death., Competing Interests: Competing interests statement:The authors declare no competing interest.

Introduction: Neonatal hypoxic-ischaemic encephalopathy (HIE) is an important illness associated with death or cerebral palsy. This study aims to assess the safety and tolerability of the allogenic human multilineage-differentiating stress-enduring cell (Muse cell)-based product (CL2020) cells in newborns with HIE. This is the first clinical trial of CL2020 cells in neonates., Methods and Analysis: This is a single-centre, open-label, dose-escalation study enrolling up to 12 patients. Neonates with HIE who receive a course of therapeutic hypothermia therapy, which cools to a body temperature of 33°C-34°C for 72 hours, will be included in this study. A single intravenous injection of CL2020 cells will be administered between 5 and 14 days of age. Subjects in the low-dose and high-dose cohorts will receive 1.5 and 15 million cells per dose, respectively. The primary outcome is the occurrence of any adverse events within 12 weeks after administration. The main secondary outcome is the Bayley Scales of Infant and Toddler Development Third Edition score and the developmental quotient per the Kyoto Scale of Psychological Development 2001 at 78 weeks., Ethics and Dissemination: This study will be conducted in accordance with the Declaration of Helsinki and Good Clinical Practice. The Nagoya University Hospital Institutional Review Board (No. 312005) approved this study on 13 November 2019. The results of this study will be published in peer-reviewed journal and reported in international conferences., Trial Registration Numbers: NCT04261335, jRCT2043190112., Competing Interests: Competing interests: SSh, MM, and YS have collaborative projects with research funding from LSII for perinatal diseases. SSh and AH receive fees based on a consultation contract from LSII. SSh, TS, MM, MH, and YS have a patent for the application of Muse cells in the treatment of HIE and other indications. LSII provided CL2020 for this clinical trial free of charge., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

We report a rare case of brain metastasis from ampullary carcinoma. A 61-year-old woman who had a past history of ampullary carcinoma surgically treated two year previously, presented with symptoms of left visual disturbance and left hemiparesis. Brain magnetic resonance images demonstrated a right occipital lobe tumor with peritumoral edema and midline shift. Gross total resection was carried out. Pathological diagnosis was poorly differentiated adenocarcinoma with compartments of signet-ring cell carcinoma. Metastases outside the abdominal cavity are rare. Brain metastases from ampullary carcinomas are extremely rare and there are few reports about such cases.

A 56-year-old woman presented with a cystic skull lesion in the right temporal bone detected after resection of breast cancer. She underwent resection of the skull tumor for pathological diagnosis and treatment. The tumor was covered with ciliated epithelium and there were no malignant findings. The pathological diagnosis was ciliated epithelial inclusion cyst. Intradiploic inclusion cysts of the skull presenting as a calvarial defect include epidermoid cysts and dermoid cysts, which are clinically difficult to differentiate. Ciliated epithelium lining an intradiploic inclusion cyst is very rare. Surgical resection is essential for a definitive diagnosis and differentiation from a neoplasm.

Pendant rotaxane switch-tethering poly(m-phenylene diethynylene) was synthesized by the polyoxidative coupling of a rotaxane containing an axle-terminal m-diethynylbenzene group and an optically active crown ether. The reversible helix-random coil transition of the polymer was successfully performed by the positional switching of the rotaxane wheel.

Neuromyelitis optica (NMO) is a relapsing inflammatory disease of the central nervous system, usually affecting the optic nerves and the spinal cord. It is presumed to be an antibody-mediated disorder and the target antigen is the water channel aquaporin-4 (AQP4) on astrocyte cell membranes. NMO is a disease caused by astrocyte disorder and is distinct from multiple sclerosis (MS), which is a primarily demyelinating disease caused by oligodendrocyte disorder. In NMO, spinal MRI shows a T2-hyperintense, longitudinally extensive (≥ 3 vertebral segments) spinal cord lesion. The case, which has optic neuritis or transverse myelitis with the presence of AQP4 antibody, is called as NMO spectrum disorder. A 68 year-old woman with a history of hypertension and diabetes mellitus was brought to the former hospital by ambulance with acute onset of tetraparesis. She denied visual acuity disturbance. MRI revealed a T2-hyperintense lesion from C5 to T2 level. Laboratory examination showed the presence of AQP4 antibody and the absence of oligoclonal bands. Low-dose steroid treatment was started after establishing a diagnosis of NMO. She incompletely recovered from disability, although the T2-hyperintense lesion on MRI had almost disappeared six months after the onset. It is important to maintain a high index of suspicion for NMO in cases with a longitudinally extensive spinal cord lesion, because untreated NMO leads to severe disability.

The crystal structure of PurL from Thermus thermophilus HB8 (TtPurL; TTHA1519) was determined in complex with an adenine nucleotide, PO(4)(3-) and Mg(2+) at 2.35 Å resolution. TtPurL consists of 29 α-helices and 28 β-strands, and one loop is disordered. TtPurL consists of four domains, A1, A2, B1 and B2, and the structures of the A1-B1 and A2-B2 domains were almost identical to each other. Although the sequence identity between TtPurL and PurL from Thermotoga maritima (TmPurL) is higher than that between TtPurL and the PurL domain of the large PurL from Salmonella typhimurium (StPurL), the secondary structure of TtPurL is much more similar to that of StPurL than to that of TmPurL., (© 2012 International Union of Crystallography. All rights reserved.)

Versatile functionalization of a crown ether/sec-ammonium salt-type rotaxane was accomplished. The rotaxane underwent reductive N-alkylation with sodium tri(acyloxy)borohydride or sodium tri(acyloxy)borohydride/arbitrary aldehyde in excellent yields. Structural switching based on reversible tert-ammonium/tert-amine conversion by acid and base was demonstrated as a pH-controlled molecular shuttle.

A 31-year-old female presented with a particularly rare hemangiopericytoma (HPC) in the right lateral ventricle manifesting as a 6-month history of visual disturbance and headache. Left hemianopsia and choked disc were identified by an ophthalmologist who referred her to us. Magnetic resonance imaging demonstrated a 5-cm homogeneously enhanced mass in the trigone of the right lateral ventricle. The tumor was totally removed by two stage surgery. The histological findings were consistent with HPC. HPC is very important to differentiate from meningioma and solitary fibrous tumors because HPC is more aggressive. The histological and immunochemical findings are important for the differential diagnosis. The present case showed no local recurrence or metastasis without radiation therapy for 4 years, indicating that radiation therapy is not absolutely imperative for patients with intraventricular HPC showing low MIB-1 staining index after total removal.