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Background: Drug resistance remains a significant impediment in leukemia treatment. While Bendamustine hydrochloride (BH) stands out as a promising therapeutic agent for non-Hodgkin's lymphoma and mantle cell lymphoma, the mechanisms of resistance to BH are not yet fully understood. Our study focuses on elucidating the mechanisms behind bendamustine resistance in leukemia cells, with a specific emphasis on epigenetics., Methods: Bendamustine-resistant cells were cultivated from human B cell lymphoblastic leukemia cell lines through systematic and sustained exposure to bendamustine, using the limiting dilution method. Gene expression was assessed via real-time polymerase chain reaction, while the expression of the multidrug resistance protein 1 (MDR1) was evaluated using flow cytometry., Results: Bendamustine-resistant leukemia cells exhibited a decreased RNA expression level for Polo-like kinase-1 (PLK-1). Notably, after treatment with the demethylating agent 5-aza-2'-deoxycytidine, PLK-1 gene expression surged significantly, enhancing bendamustine's cytotoxicity in the resistant leukemia cells. However, MDR1 expression, as determined by flow cytometry, remained consistent between parental and bendamustine-resistant leukemia cells., Conclusions: Our findings indicate that the methylation of the PLK-1 gene plays a pivotal role in modulating PLK-1 expression and is central to the development of bendamustine resistance in leukemia cells.

Background: Adipose tissue-derived mesenchymal stem cells (ADSCs) are used for the treatment of various diseases because of their rapid proliferation and high anti-inflammatory and tissue repair properties. Kawasaki disease is a systemic vasculitis with coronary arteritis and aneurysms occurring in pediatric patients. In this study, we examined serologically and pathologically whether the administration of human ADSCs (hADSCs) to a mouse model of Kawasaki disease could suppress vasculitis., Methods: Candida albicans water-soluble fractions were intraperitoneally injected into DBA/2 mice for 5 consecutive days to generate a mouse model of Kawasaki disease. The model mice were intravenously administered hADSCs or phosphate-buffered saline (PBS). Serum samples collected on days 15 and 29 were used to compare cytokine levels. Mouse hearts dissected on day 29 were subjected to hematoxylin and eosin and immunohistological staining using Galectin-1 (Gal-1), a protein involved in cardiovascular homeostasis, and CD44, a cell-surface marker of hADSCs., Results: Comparison of inflammation-related cytokines showed a significant decrease in IL-1α expression at day 15 (P<0.05) and IL-6 expression at day 29 (P<0.01) in the hADSCs-treated group compared to the PBS group. Evaluation by hematoxylin and eosin staining showed decreased inflammatory cell infiltration and a tendency towards increased Gal-1 expression in the hADSCs group. CD44 expression was not observed in both the groups. The survival curve showed that the hADSCs group had a significantly longer survival time (P<0.05)., Conclusions: The present experimental results indicate that hADSCs have an early anti-inflammatory effect, and that Gal-1 may be involved in preventing inflammation and reducing tissue damage.

The patient was a 3-year-old girl whose father was employed sorting and washing soybeans. She exhibited transient respiratory distress and loss of activity on the same day or the next day after her father came home wearing work clothes with soybean dust on them. One day, she developed anaphylaxis after being lifted into her father's arms while he was wearing his work clothes. Although a blood test was positive for soybean and Gly m 4-specific IgE antibodies, the girl was able to consume soy products (not including soy milk, which she had never consumed) without any issues. The father was instructed to change clothes before leaving work and bathe immediately upon returning home, and the girl has not had any further episodes of respiratory distress, loss of activity, or anaphylaxis. Though reports of anaphylaxis from soybean antigen inhalation are extremely rare, it is very likely that inhalation of soybean dust from the father's work clothes induced anaphylaxis in this case.

Immotile cilia at the ventral node of mouse embryos are required for sensing leftward fluid flow that breaks left-right symmetry of the body. However, the flow-sensing mechanism has long remained elusive. In this work, we show that immotile cilia at the node undergo asymmetric deformation along the dorsoventral axis in response to the flow. Application of mechanical stimuli to immotile cilia by optical tweezers induced calcium ion transients and degradation of Dand5 messenger RNA (mRNA) in the targeted cells. The Pkd2 channel protein was preferentially localized to the dorsal side of immotile cilia, and calcium ion transients were preferentially induced by mechanical stimuli directed toward the ventral side. Our results uncover the biophysical mechanism by which immotile cilia at the node sense the direction of fluid flow.

Dinitrogen is an abundant and promising material for valuable organonitrogen compounds containing carbon-nitrogen bonds. Direct synthetic methods for preparing organonitrogen compounds from dinitrogen as a starting reagent under mild reaction conditions give insight into the sustainable production of valuable organonitrogen compounds with reduced fossil fuel consumption. Here we report the catalytic reaction for the formation of cyanate anion (NCO - ) from dinitrogen under ambient reaction conditions. A molybdenum-carbamate complex bearing a pyridine-based 2,6-bis(di-tert-butylphosphinomethyl)pyridine (PNP)-pincer ligand is synthesized from the reaction of a molybdenum-nitride complex with phenyl chloroformate. The conversion between the molybdenum-carbamate complex and the molybdenum-nitride complex under ambient reaction conditions is achieved. The use of samarium diiodide (SmI 2 ) as a reductant promotes the formation of NCO - from the molybdenum-carbamate complex as a key step. As a result, we demonstrate a synthetic cycle for NCO - from dinitrogen mediated by the molybdenum-PNP complexes in two steps. Based on this synthetic cycle, we achieve the catalytic synthesis of NCO - from dinitrogen under ambient reaction conditions., (© 2022. The Author(s).)

Sexual reproduction is widespread in eukaryotes; however, only asexual reproduction has been observed in unicellular red algae, including Galdieria , which branched early in Archaeplastida. Galdieria possesses a small genome; it is polyextremophile, grows either photoautotrophically, mixotrophically, or heterotrophically, and is being developed as an industrial source of vitamins and pigments because of its high biomass productivity. Here, we show that Galdieria exhibits a sexual life cycle, alternating between cell-walled diploid and cell wall-less haploid, and that both phases can proliferate asexually. The haploid can move over surfaces and undergo self-diploidization or generate heterozygous diploids through mating. Further, we prepared the whole genome and a comparative transcriptome dataset between the diploid and haploid and developed genetic tools for the stable gene expression, gene disruption, and selectable marker recycling system using the cell wall-less haploid. The BELL/KNOX and MADS-box transcription factors, which function in haploid-to-diploid transition and development in plants, are specifically expressed in the haploid and diploid, respectively, and are involved in the haploid-to-diploid transition in Galdieria , providing information on the missing link of the sexual life cycle evolution in Archaeplastida. Four actin genes are differently involved in motility of the haploid and cytokinesis in the diploid, both of which are myosin independent and likely reflect ancestral roles of actin. We have also generated photosynthesis-deficient mutants, such as blue-colored cells, which were depleted in chlorophyll and carotenoids, for industrial pigment production. These features of Galdieria facilitate the understanding of the evolution of algae and plants and the industrial use of microalgae.

When protons and neutrons (nucleons) are bound into atomic nuclei, they are close enough to feel significant attraction, or repulsion, from the strong, short-distance part of the nucleon-nucleon interaction. These strong interactions lead to hard collisions between nucleons, generating pairs of highly energetic nucleons referred to as short-range correlations (SRCs). SRCs are an important but relatively poorly understood part of nuclear structure 1-3 , and mapping out the strength and the isospin structure (neutron-proton (np) versus proton-proton (pp) pairs) of these virtual excitations is thus critical input for modelling a range of nuclear, particle and astrophysics measurements 3-5 . Two-nucleon knockout or 'triple coincidence' reactions have been used to measure the relative contribution of np-SRCs and pp-SRCs by knocking out a proton from the SRC and detecting its partner nucleon (proton or neutron). These measurements 6-8 have shown that SRCs are almost exclusively np pairs, but they had limited statistics and required large model-dependent final-state interaction corrections. Here we report on measurements using inclusive scattering from the mirror nuclei hydrogen-3 and helium-3 to extract the np/pp ratio of SRCs in systems with a mass number of three. We obtain a measure of the np/pp SRC ratio that is an order of magnitude more precise than previous experiments, and find a marked deviation from the near-total np dominance observed in heavy nuclei. This result implies an unexpected structure in the high-momentum wavefunction for hydrogen-3 and helium-3. Understanding these results will improve our understanding of the short-range part of the nucleon-nucleon interaction., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Clear-cell sarcoma of the kidney (CCSK) is a rare, aggressive pediatric renal tumor. Intratumoral hemorrhage and tumor rupture are oncologic emergencies requiring a rapid and appropriate response. An 11-year-old boy visited our hospital with abdominal distension of 1 month's duration. Computed tomography (CT) revealed a tumor in the left kidney (size: 200 mm), and analysis of a biopsy specimen confirmed a diagnosis of CCSK. Chemotherapy was initiated to shrink the large, densely vascularized tumor before surgical removal. Two days after starting chemotherapy, the patient developed abdominal and back pain, anemia, and hypotension. CT scanning showed intratumoral bleeding. Emergency transcatheter arterial embolization (TAE) was performed to control the bleeding. Three tumor feeding vessels were identified: an ascending branch from the celiac artery, an intermediate branch from the left renal artery, and a descending branch from the inferior mesenteric artery, of which the intermediate and descending branches were large and bleeding profusely. Therefore, the intermediate branch was injected with ethanol, and the descending branch was treated by gel-foam embolization. Chemotherapy was resumed, and the patient's condition gradually stabilized. The tumor began to shrink, and subsequent chemotherapy progressed well. In week 12 of chemotherapy, the patient underwent tumor resection and left nephrectomy. Postoperative chemotherapy was completed without complications, and there was no recurrence during a 6-year follow-up period. Therefore, TAE can effectively control intratumoral bleeding in pediatric solid tumors, thus preventing high-risk open surgery.

Spatial active noise control (ANC) systems focus on minimizing unwanted acoustic noise over continuous spatial regions by generating anti-noise fields with secondary loudspeakers. Conventionally, error microphones are necessary inside the region to measure the channels from the secondary loudspeakers to the error microphones and record the residual sound field during the noise control. These error microphones highly limit the implementation of spatial ANC systems because of their impractical geometry and obstruction to the users from accessing the region. Recent advances, such as virtual sensing, focus on ANC with microphones placed away from the region. While these techniques relax the usage of error microphones during the noise control, an error microphone array remains necessary during the secondary channel estimation. In this paper, we propose a method to estimate secondary channels without using an error microphone array. Instead, a moving higher order microphone is applied to obtain the secondary channels from the secondary loudspeakers to the region of interest, which includes all desired error microphone locations. By simulation, we show that the proposed method is robust against various measuring errors introduced by the movement of the microphone and is suitable for the secondary channel estimation in spatial ANC systems.

A molybdenum-nitride complex bearing a pyridine-based PNP-type pincer ligand derived from dinitrogen is reacted with various kinds of carbon-centered electrophiles to functionalize the nitride ligand in the molybdenum complex. Methylation with MeOTf and acylation with diphenylacetyl chloride of the nitride complex afford the corresponding imide complexes via a carbon-nitrogen bond formation. In the case of reactions with phenylisocyanate and diphenylketene, the PNP ligand works as a non-innocent ligand to form the corresponding ureate and acylimide complexes, respectively. These newly synthesized complexes are characterized by X-ray analysis. As a further transformation of the prepared imide complexes, hydrolysis of the molybdenum-acylimide complex proceeds to give the corresponding amide as an organonitrogen compound together with the corresponding molybdenum-oxo complex. This result indicates that the nitrogen molecule is converted into organic amide mediated by the molybdenum-nitride complex.

Assessing long-term changes in the biomass of old-growth forests with consideration of climate effects is essential for understanding forest ecosystem functions under a changing climate. Long-term biomass changes are the result of accumulated short-term changes, which can be affected by endogenous processes such as gap filling in small-scale canopy openings. Here, we used 26 years (1993-2019) of repeated tree census data in an old-growth, cool-temperate, mixed deciduous forest that contains three topographic units (riparian, denuded slope, and terrace) in northern Japan to document decadal changes in aboveground biomass (AGB) and their processes in relation to endogenous processes and climatic factors. AGB increased steadily over the 26 years in all topographic units, but different tree species contributed to the increase among the topographic units. AGB gain within each topographic unit exceeded AGB loss via tree mortality in most of the measurement periods despite substantial temporal variation in AGB loss. At the local scale, variations in AGB gain were partially explained by compensating growth of trees around canopy gaps. Climate affected the local-scale AGB gain: the gain was larger in the measurement periods with higher mean air temperature during the current summer but smaller in those with higher mean air temperature during the previous autumn, synchronously in all topographic units. The influences of decadal summer and autumn warming on AGB growth appeared to be counteracting, suggesting that the observed steady AGB increase in KRRF is not fully explained by the warming. Future studies should consider global and regional environmental factors such as elevated CO 2 concentrations and nitrogen deposition, and include cool-temperate forests with a broader temperature range to improve our understanding on biomass accumulation in this type of forests under climate change., (© 2021. The Author(s).)

Galectins are β-galactoside-binding lectins consisting of 15 members in mammals. Galectin-1,-3,-4,-8, and -9 are predominantly expressed in the central nervous system (CNS) and regulate various physiological and pathological events. This review summarizes the current knowledge of the cellular expression and role of galectins in the CNS, and discusses their functions in neurite outgrowth, myelination, and neural stem/progenitor cell niches, as well as in ischemic/hypoxic/traumatic injuries and neurodegenerative diseases such as multiple sclerosis. Galectins are expressed in both neurons and glial cells. Galectin-1 is mainly expressed in motoneurons, whereas galectin-3-positive neurons are broadly distributed throughout the brain, especially in the hypothalamus, indicating its function in the regulation of homeostasis, stress response, and the endocrine/autonomic system. Astrocytes predominantly contain galectin-1, and galectin-3 and-9 are upregulated along with its activation. Activated, but not resting, microglia contain galectin-3, supporting its phagocytic activity. Galectin-1,-3, and -4 are characteristically expressed during oligodendrocyte differentiation. Galectin-3 from microglia promotes oligodendrocyte differentiation and myelination, while galectin-1 and axonal galectin-4 suppress its differentiation and myelination. Galectin-1- and- 3-positive cells are involved in neural stem cell niche formation in the subventricular zone and hippocampal dentate gyrus, and the migration of newly generated neurons and glial cells to the olfactory bulb or damaged lesions. In neurodegenerative diseases, galectin-1,-8, and -9 have neuroprotective and anti-inflammatory activities. Galectin-3 facilitates pro-inflammatory action; however, it also plays an important role during the recovery period. Several ligand glycoconjugates have been identified so far such as laminin, integrins, neural cell adhesion molecule L1, sulfatide, neuropilin-1/plexinA4 receptor complex, triggering receptor on myeloid cells 2, and T cell immunoglobulin and mucin domain. N -glycan branching on lymphocytes and oligodendroglial progenitors mediated by β1,6- N -acetylglucosaminyltransferase V (Mgat5/GnTV) influences galectin-binding, modulating inflammatory responses and remyelination in neurodegenerative diseases. De-sulfated galactosaminoglycans such as keratan sulfate are potential ligands for galectins, especially galectin-3, regulating neural regeneration. Galectins have multitudinous functions depending on cell type and context as well as post-translational modifications, including oxidization, phosphorylation, S-nitrosylation, and cleavage, but there should be certain rules in the expression patterns of galectins and their ligand glycoconjugates, possibly related to glucose metabolism in cells., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Nio-Kobayashi and Itabashi.)

Objective: To prospectively examine whether laminoplasty with maximal expansion induces C5 palsy, even with prophylactic bilateral C4/5 foraminotomy., Methods: Thirty-five consecutive patients with cervical myelopathy underwent laminoplasty (n = 19: LP group) or posterior decompression and fusion (n = 16: PDF group) with maximal expansion. Prophylactic bilateral C4/5 foraminotomy was performed alternately in consecutive five patients undergoing each type of surgery. In each type of surgery, the first and third consecutive five patients did not undergo foraminotomy (NF subgroup: 20 patients), while the second and fourth consecutive five patients underwent foraminotomy (F subgroup: 15 patients). The widths between the gutters was equivalent to the diameter of the spinal canal, and an inclination angle of the lamina of approximately 90° was created during laminoplasty. The incidence and severity of postoperative C5 palsy were investigated. Patients with a manual muscle testing score for the deltoid muscle and/or biceps brachii muscle of ≤ 2 were diagnosed with severe palsy., Results: The respective incidences of C5 palsy in the F and NF subgroups were 33% and 20% in the LP group and 50% and 20% in the PDF group. Severe palsy occurred in 67% and 0% of patients who had developed palsy in F and NF subgroups, respectively, in the LP group, and in 100% of patients in the PDF group. Furthermore, 40% of the patients with severe palsy took more than 6 months to recover., Conclusions: Laminoplasty with maximal expansion induced C5 palsy in both the LP and PDF groups, even with the addition of prophylactic bilateral C4/5 foraminotomy., (© 2020. Springer-Verlag France SAS, part of Springer Nature.)

In vegetables of Brassica rapa L., Fusarium oxysporum f. sp. rapae ( For ) or F. oxysporum f. sp. conglutinans ( Foc ) cause Fusarium yellows. A resistance gene against Foc ( FocBr1 ) has been identified, and deletion of this gene results in susceptibility ( focbr1-1 ). In contrast, a resistance gene against For has not been identified. Inoculation tests showed that lines resistant to Foc were also resistant to For , and lines susceptible to Foc were susceptible to For . However, prediction of disease resistance by a dominant DNA marker on FocBr1 (Bra012688m) was not associated with disease resistance of For in some komatsuna lines using an inoculation test. QTL-seq using four F 2 populations derived from For susceptible and resistant lines showed one causative locus on chromosome A03, which covers FocBr1 . Comparison of the amino acid sequence of FocBr1 between susceptible and resistant alleles ( FocBr1 and FocBo1 ) showed that six amino acid differences were specific to susceptible lines. The presence and absence of FocBr1 is consistent with For resistance in F 2 populations. These results indicate that FocBr1 is essential for For resistance, and changed amino acid sequences result in susceptibility to For . This susceptible allele is termed focbr1-2 , and a new DNA marker (focbr1-2m) for detection of the focbr1-2 allele was developed.

A 72-year-old woman was admitted to our hospital because of symptoms of bleeding diathesis such as hematuria and purpura. A blood test revealed disseminated intravascular coagulation(DIC). Upper gastrointestinal endoscopy showed advanced gastric cancer. Bone marrow aspiration cytology demonstrated diffuse hyperplasia of large atypical cells, and metastasis of the epithelial tumor was suspected on immunohistochemical examination. She was diagnosed with disseminated carcinomatosis of the bone marrow associated with gastric cancer accompanied by DIC. She was treated with weekly infusion of methotrexate 100 mg/m2 plus 5-fluorouracil 600 mg/m2 for 4 courses; and she completely recovered from DIC. She received oral tegafur/gimeracil/oteracil as an outpatient. However, DIC recurred 126 days after the initial chemotherapy, and 5-fluorouracil plus cisplatin was administered subsequently. After 1 course, she died 166 days after the initial chemotherapy. Although the prognosis of patients with disseminated carcinomatosis of the bone marrow associated with gastric cancer accompanied by DIC is extremely poor, this case shows that secession of DIC and prognostic improvement by chemotherapy could occur. Chemotherapy could be considered a potentially effective treatment in this case.

Purpose of Review: Coronavirus disease 2019 (COVID-19), a respiratory infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 virus), is a pandemic in over 120 countries worldwide. Risk factors for severe COVID-19 include older age, ethnicity, sex, comorbidities, and living conditions. Although asthmatics and those with allergies are susceptible to more severe outcomes to viral infections, interestingly, asthma has not been reported to be a major comorbidity of COVID-19. However, there are some conflicting reports on the impact of asthma on COVID-19. The underlying immunological and molecular mechanisms may explain at least in part these observations. Furthermore, environmental factors like air pollution that have detrimental effects on asthma and respiratory illnesses also have an impact on COVID-19., Recent Findings: Angiotensin-converting enzyme 2 (ACE2) is the receptor for the attachment and entry of SARS-CoV-2 into the host cells that is upregulated by Th1-mediated responses. In asthmatics, ACE2 gene expression is generally reduced and recent studies have shown a negative correlation between the levels of Th2 cytokines including IL-4, IL-5, and IL-13 in airway epithelial cells and other type 2 biomarkers with ACE2 expression. This may explain in part the potential protective role of asthma on COVID-19. Here, we review the relation of respiratory viral illnesses and asthma, the immune-molecular mechanisms of SARS-CoV-2 infection, the impact of asthma on COVID-19 and that of SARS-CoV-2 on asthma and allergic rhinitis, and the impact of environmental factors like air pollution on COVID-19., Summary: Expression of ACE2 in airway epithelial cells in SARS-COV-2 is influenced by inflammatory profile. Respiratory allergic diseases like asthma appear to have a protective effect against SARS-COV-2 infection. However, the clinical association between asthma and SARS-COV-2 is not fully established and the underlying immune-molecular mechanisms may explain these observations., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: The purpose of the present study was to compare the treatment success rates of primary neurosurgical and endovascular treatments in patients with spinal dural arteriovenous fistulas (dAVFs)., Methods: Data from 199 consecutive patients with thoracic and lumbosacral spinal dAVFs were collected from 18 centers. Angiographic and clinical findings, the rate of initial treatment failure or recurrence by procedures, risk factors for treatment failure, complications, and neurological outcomes were statistically analyzed., Results: Spinal dAVFs were frequently detected in the thoracic region (81%), fed by a single feeder (86%), and shunted into an intradural vein via the dura mater. The fistulous connection between the feeder(s) and intradural vein was located at a single spinal level in 195 patients (98%) and at 2 independent levels in 4 patients (2%). Among the neurosurgical (n = 145), and endovascular (n = 50) treatment groups of single dAVFs (n = 195), the rate of initial treatment failure or recurrence was significantly higher in the index endovascular treatment group (0.68% and 36%). A multivariate analysis identified endovascular treatment as an independent risk factor with significantly higher odds of initial treatment failure or recurrence (OR 69; 95% CI 8.7-546). The rate of complications did not significantly differ between the two treatment groups (4.1% for neurosurgical vs 4.0% for endovascular treatment). With a median follow-up of 26 months, improvements of ≥ 1 point in the modified Rankin Scale (mRS) score and Aminoff-Logue gait and Aminoff-Logue micturition grades were observed in 111 (56%), 121 (61%), and 79 (40%) patients, respectively. Independent risk factors for lack of improvement in the Aminoff-Logue gait grades were multiple treatments due to initial treatment failure or recurrence (OR 3.1) and symptom duration (OR 1.02)., Conclusions: Based on data obtained from the largest and most recently assessed multicenter cohort, the present study shows that primary neurosurgery is superior to endovascular treatment for the complete obliteration of spinal dAVFs by a single procedure.

Fibrous collagen imparts physical strength and flexibility to tissues by forming huge complexes. The density and orientation of collagen fibers must be correctly specified for the optimal physical property of the collagen complex. However, little is known about its underlying cellular mechanisms. Actinotrichia are collagen fibers aligned at the fin-tip of bony fish and are easily visible under the microscope due to their thick, linear structure. We used the actinotrichia as a model system to investigate how cells manipulate collagen fibers. The 3D image obtained by focused ion beam scanning electron microscopy (FIB-SEM) showed that the pseudopodia of mesenchymal cells encircle the multiple actinotrichia. We then co-incubated the mesenchymal cells and actinotrichia in vitro , and time-lapse analysis revealed how cells use pseudopods to align collagen fiber orientation. This in vitro behavior is dependent on actin polymerization in mesenchymal cells. Inhibition of actin polymerization in mesenchymal cells results in mis-orientation of actinotrichia in the fin. These results reveal how mesenchymal cells are involved in fin formation and have important implications for the physical interaction between cells and collagen fibers., (Copyright © 2020 Kuroda, Itabashi, Iwane, Aramaki and Kondo.)

Immotile cilia sense extracellular signals such as fluid flow, but whether Ca 2+ plays a role in flow sensing has been unclear. Here, we examined the role of ciliary Ca 2+ in the flow sensing that initiates the breaking of left-right (L-R) symmetry in the mouse embryo. Intraciliary and cytoplasmic Ca 2+ transients were detected in the crown cells at the node. These Ca 2+ transients showed L-R asymmetry, which was lost in the absence of fluid flow or the PKD2 channel. Further characterization allowed classification of the Ca 2+ transients into two types: cilium-derived, L-R-asymmetric transients (type 1) and cilium-independent transients without an L-R bias (type 2). Type 1 intraciliary transients occurred preferentially at the left posterior region of the node, where L-R symmetry breaking takes place. Suppression of intraciliary Ca 2+ transients delayed L-R symmetry breaking. Our results implicate cilium-derived Ca 2+ transients in crown cells in initiation of L-R symmetry breaking in the mouse embryo., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)

Hemophagocytic lymphohistiocytosis (HLH) associated with Epstein-Barr virus (EBV) infection can be self-limiting, severe/aggressive, or fatal. We report a case of EBV-HLH with persistent fever, severe pancytopenia, hypertriglyceridemia, and hypofibrinogenemia in a 4-year-old boy. Levels of plasma cytokines and chemokines were measured with a Bio-Plex system at 1, 2, 3, 4, 5, and 8 days after hospital admission. Administration of steroid and high-dose intravenous immunoglobulin (1 g/kg) did not alleviate fever or reduce cytokine production; however, after administration of etoposide (an antineoplastic agent), fever decreased immediately, the patient's general condition improved, and levels of IL-6, IL-10, IL-8, MCP-1, IFN-γ, and TNF-α declined after etoposide administration. In particular, IFN-γ production sharply declined, from 1,104.1 pg/mL to 101.5 pg/mL, and IL-6 level decreased from 229.8 pg/mL to 11.0 pg/mL, on the day after initial etoposide administration. There was no later recurrence of symptoms during treatment with dexamethasone, etoposide, and cyclosporine A. This case suggests that early etoposide administration is critical for treatment success and indicates that etoposide promptly inhibits cytokine production.

Primary cilia are antenna-like organelles on the surface of most mammalian cells that receive sonic hedgehog (Shh) signaling in embryogenesis and carcinogenesis. Cellular cholesterol functions as a direct activator of a seven-transmembrane oncoprotein called Smoothened (Smo) and thereby induces Smo accumulation on the ciliary membrane where it transduces the Shh signal. However, how cholesterol is supplied to the ciliary membrane remains unclear. Here, we report that peroxisomes are essential for the transport of cholesterol into the ciliary membrane. Zellweger syndrome (ZS) is a peroxisome-deficient hereditary disorder with several ciliopathy-related features and cells from these patients showed a reduced cholesterol level in the ciliary membrane. Reverse genetics approaches revealed that the GTP exchange factor Rabin8, the Rab GTPase Rab10, and the microtubule minus-end-directed kinesin KIFC3 form a peroxisome-associated complex to control the movement of peroxisomes along microtubules, enabling communication between peroxisomes and ciliary pocket membranes. Our findings suggest that insufficient ciliary cholesterol levels may underlie ciliopathies., (© 2020 The Authors. Published under the terms of the CC BY NC ND 4.0 license.)

Objective: Spinal arteriovenous shunts are rare vascular lesions and are classified into 4 types (types I-IV). Due to rapid advances in neuroimaging, spinal epidural AVFs (edAVFs), which are similar to type I spinal dural AVFs (dAVFs), have recently been increasingly reported. These 2 entities have several important differences that influence the treatment strategy selected. The purposes of the present study were to compare angiographic and clinical differences between edAVFs and dAVFs and to provide treatment strategies for edAVFs based on a multicenter cohort., Methods: A total of 280 consecutive patients with thoracic and lumbosacral spinal dural arteriovenous fistulas (dAVFs) and edAVFs with intradural venous drainage were collected from 19 centers. After angiographic and clinical comparisons, the treatment failure rate by procedure, risk factors for treatment failure, and neurological outcomes were statistically analyzed in edAVF cases., Results: Final diagnoses after an angiographic review included 199 dAVFs and 81 edAVFs. At individual centers, 29 patients (36%) with edAVFs were misdiagnosed with dAVFs. Spinal edAVFs were commonly fed by multiple feeding arteries (54%) shunted into a single or multiple intradural vein(s) (91% and 9%) through a dilated epidural venous plexus. Preoperative modified Rankin Scale (mRS) and Aminoff-Logue gait and micturition grades were worse in patients with edAVFs than in those with dAVFs. Among the microsurgical (n = 42), endovascular (n = 36), and combined (n = 3) treatment groups of edAVFs, the treatment failure rate was significantly higher in the index endovascular treatment group (7.5%, 31%, and 0%, respectively). Endovascular treatment was found to be associated with significantly higher odds of initial treatment failure (OR 5.72, 95% CI 1.45-22.6). In edAVFs, the independent risk factor for treatment failure after microsurgery was the number of intradural draining veins (OR 17.9, 95% CI 1.56-207), while that for treatment failure after the endovascular treatment was the number of feeders (OR 4.11, 95% CI 1.23-13.8). Postoperatively, mRS score and Aminoff-Logue gait and micturition grades significantly improved in edAVFs with a median follow-up of 31 months., Conclusions: Spinal epidural AVFs with intradural venous drainage are a distinct entity and may be classified as type V spinal vascular malformations. Based on the largest multicenter cohort, this study showed that primary microsurgery was superior to endovascular treatment for initial treatment success in patients with spinal edAVFs.

Assessing the structure and function of organelles in living organisms of the primitive unicellular red algae Cyanidioschyzon merolae on three-dimensional sequential images demands a reliable automated technique in the class imbalance among various cellular structures during mitosis. Existing classification networks with commonly used loss functions were focused on larger numbers of cellular structures that lead to the unreliability of the system. Hence, we proposed a balanced deep regularized weighted compound dice loss (RWCDL) network for better localization of cell organelles. Specifically, we introduced two new loss functions, namely compound dice (CD) and RWCD by implementing multi-class variant dice and weighting mechanism, respectively for maximizing weights of peroxisome and nucleus among five classes as the main contribution of this study. We extended the Unet-like convolution neural network (CNN) architecture for evaluating the ability of our proposed loss functions for improved segmentation. The feasibility of the proposed approach is confirmed with three different large scale mitotic cycle data set with different number of occurrences of cell organelles. In addition, we compared the training behavior of our designed architectures with the ground truth segmentation using various performance measures. The proposed balanced RWCDL network generated the highest area under the curve (AUC) value in elevating the small and obscure peroxisome and nucleus, which is 30% higher than the network with commonly used mean square error (MSE) and dice loss (DL) functions. The experimental results indicated that the proposed approach can efficiently identify the cellular structures, even when the contour between the cells is obscure and thus convinced that the balanced deep RWCDL approach is reliable and can be helpful for biologist to accurately identify the relationship between the cell behavior and structures of cell organelles during mitosis.

A large amount of excavated soils with low-level As contamination caused by civil construction projects is of great concern in Japan. This study investigated the chemical speciation and extractability of As in 24 soil samples from the sites affected and unaffected (naturally contaminated) by anthropogenic pollution. The results of As K-edge XANES demonstrated that naturally contaminated soils were grouped into two types: (i) soils containing FeAsS-like and As 2 S 3 -like species (ave. 53%, hereafter As-S species) and (ii) soils with no or minor As-S species (ave. 3%). Clear differences were found in As, Fe, and S fractionations by sequential extraction. From naturally contaminated soils enriched with As-S species, more than 50% of As was extracted in the oxidizable fraction. Arsenic was mainly recovered in the reducible fraction for naturally contaminated soils with no or minor As-S species and anthropogenically contaminated soils. The μ-XRF and μ-XAFS revealed that the naturally contaminated soils containing As-S species were abundant in pyrite framboids (∼20 μm in diameter) in which As occurred as multiple oxidation states. The results suggest that framboidal pyrite becomes a source of As in naturally contaminated soils after being excavated and exposed to the surface environment.

A case of a vascular complication after collagenase injection and manipulation for Dupuytren's contracture in a 57-year-old Japanese man is described. The patient presented with a 10-year history of worsening primary Dupuytren's contracture. The metacarpophalangeal joint of his left little finger had a flexion contracture of 40° and was treated by collagenase injection. When the patient returned to our hospital for manipulation 24 hours later, however, his left little finger was almost completely improved because he hit his finger on the car's gear lever. Then, 9 months after collagenase injection, in the first winter, he complained of a painful and pale left little finger occurring a few times a day, lasting for about 10 minutes. Now, two years after collagenase injection, the episodes of Raynaud's phenomenon remain. Although Raynaud's phenomenon after collagenase injection and manipulation for Dupuytren's contracture is considered rare, it is a complication to be noted., Competing Interests: None, (Copyright © Japan Medical Association.)

Background: Therapeutic outcomes for childhood malignancy have dramatically improved. However, secondary malignancies are a major concern, as they greatly affect the quality of life of survivors. This retrospective study evaluated the cumulative incidence, clinical features, and outcomes of secondary malignancies at Nippon Medical School Hospital., Methods: We examined data from 275 cases of primary childhood malignancy diagnosed between 1980 and 2014. Information regarding treatment of the primary malignancy, including irradiation dose, site, and cumulative dose of anticancer drugs, was assessed. We also collected data on secondary malignancy, including patient sex, age at diagnosis, malignancy site, time from primary to secondary malignancy, and outcomes., Results: Secondary malignancies developed in 11 patients and included acute myeloid leukemia (AML) (4), meningioma (4), Ewing sarcoma (1), germ cell tumor (1), and malignant parotid gland tumor (1). The primary malignancies included acute lymphoblastic leukemia (ALL) (9), non-Hodgkin lymphoma (1) and brain tumor (1). In 7 of the 9 ALL patients, chemoradiotherapy was the primary treatment. The meningiomas and 1 solid tumor developed within the radiation field. All AMLs and meningiomas developed within 5 years and after 20 years, respectively, of the primary diagnosis. The 10- and 20-year cumulative incidence rates for secondary malignancy in our hospital were 1.9% and 5.8%, respectively., Conclusions: Our results revealed that the type of secondary malignancy depends on the interval after the end of treatment for primary malignancy. Meningioma, notably, develops many years after completion of primary malignancy treatment. Early detection during long-term follow-up is therefore essential.

Introduction: This retrospective study compared rates of bony fusion and screw loosening after multilevel posterior decompression and fusion (PDF) with short monocortical screws (SMS) as a novel mid-cervical anchor versus C5 pedicle screws (PS) as a mid-cervical anchor., Methods: We analyzed 15 consecutive patients who underwent C2-T1 PDF with C5 PS as mid-cervical anchor (PS group) and 18 consecutive patients who underwent the procedure with SMS at C4-C6 as mid-cervical anchor (SMS group). Radiological outcomes, including rates of bony fusion at each level and screw loosening, and clinical outcomes, including Japanese Orthopedic Association (JOA) score, neck pain, neck disability index (NDI), and EuroQol 5 Dimension (EQ-5D), were compared between groups. In the SMS group, screw perforation types and appropriate screw insertion procedure were also investigated., Results: The fusion rate at C2/3 in the SMS group (56%) was significantly higher than that in PS group (13%; P = 0.0272). None of the patients had SMS loosening postoperatively. Clinical outcomes, including JOA score, neck pain, NDI, and EQ-5D, did not differ between the groups. In the SMS group, facet perforation was the most common type of perforation. The recommended direction for SMS insertion at C4-C6 was 35°-37° in the cranial direction and 25°-30° in the medial direction; the recommended screw length was 10 mm., Conclusions: SMS at C4-C6 was as effective as C5 PS as a mid-cervical anchor in PDF, according to clinical and radiological outcomes. The fusion rate at C2/3 in the SMS group was significantly higher than that in the PS group. There was no postoperative loosening of the C5 PS or C4-C6 SMS in either group., Competing Interests: Conflicts of Interest: The authors declare that there are no relevant conflicts of interest., (Copyright © 2019 by The Japanese Society for Spine Surgery and Related Research.)

Molybdenum triiodide complexes bearing various substituted pyridine-based PNP-type pincer ligands are prepared and characterized by X-ray analysis. Their catalytic activity is investigated toward the reduction of nitrogen gas into ammonia under ambient reaction conditions.

Introduction: Fluoroscopy-guided selective nerve root block (SNRB) is useful for the diagnosis and treatment of nerve root pain. However, the procedure exposes the surgeon's hands to radiation. Therefore, the purpose of this randomized prospective study was to assess the radiation exposure per unit time of the surgeon's fingers during performance of a lumbosacral SNRB and to calculate the annual exposure time limits for four hand-protection methods., Methods: We prospectively recruited patients scheduled for an SNRB and measured the radiation exposure using a ring-type passive radiation dosimetry device attached to the distal phalanx of the index finger of the hand performing the needle placement. Patients were randomly divided into the following four groups: a) the direct exposure group, b) the 0.03-mmPb glove group, c) the 0.25-mmPb glove group, and d) the forceps group (in which the needle was held using forceps such that the fingers did not enter the irradiation field)., Results: We recruited 40 consecutive patients (16 men and 24 women), with a mean age of 69 years. In all cases, SNRB was successfully performed without complications. The average exposure per hour for each of the four groups was as follows: 0.67 ± 0.56 mSv/s in the direct exposure group, 0.12 ± 0.07 mSv/s in the 0.03-mmPb glove group, 0.019 ± 0.02 mSv/s in the 0.25-mmPb glove group, and 0.001 ± 0.004 mSv/s in the forceps group (p < 0.01). The average annual exposure time limit was 12.4 min in the direct exposure group, 67.9 min in the 0.03-mmPb glove group, 7.5 h in the 0.25-mmPb glove group, and 5.0 days in the forceps group., Conclusions: Using a radiation reduction glove or forceps greatly decreased the radiation exposure and increased the annual exposure time limit for SNRB., Competing Interests: Conflicts of Interest: The authors declare that there are no relevant conflicts of interest.

Multiple sclerosis (MS) is an autoimmune disease in which pathogenic T cells play an important role, and an experimental autoimmune encephalomyelitis (EAE) is used as an animal model of MS. Galectins are β-galactoside-binding lectins and involved in various physiological and pathological events. Among fifteen members of galectins, galectin-1, -8, and -9 play immunosuppressive roles in MS and EAE; however, the role of galectin-3 (gal-3) is complex and controversial. We examined expression of gal-3 in the spinal cord and nerve roots of EAE mice. No immunohistochemical signals were detected in naïve mice, whereas gal-3 appeared at lower lumbar levels of the spinal cord and nerve roots in EAE mice. In the spinal cord, gal-3-positive cells were activated microglia and/or infiltrating macrophages, which were round in shape and intensified for the lysosomal enzyme, cathepsin D, indicating elevated phagocytic activity. Gal-3-positive cells in the spinal cord were most abundant during the peak symptomatic period. In the recovery period, they disappeared from the spinal parenchyma but remained at moderate levels in the pia mater. Interestingly, gal-3-positive cells selectively appeared in ventral, but not dorsal, nerve roots running through the spinal canal, with expression peaking during the recovery period. In ventral nerve roots, the major cell type expressing gal-3 was a specific population of Schwann cells that surround unmyelinated axons and express the biosynthetic enzyme for l-serine, a potent neurotrophic amino acid. Gal-3 was also induced in Iba1/F4/80-positive macrophages, which engulf damaged myelin and axon debris. Thus, gal-3 is induced in distinct cell types that are engaged in removal of damaged axons and cell debris and axon regeneration and remyelination, suggesting a potential neuroprotective role of gal-3 in EAE mice., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Purpose: To present a novel posterior approach in multilevel cervical posterior decompression and fusion (PDF) using C2 pedicle screws that preserves the rectus capitis posterior major, oblique capitis inferior, and semispinalis cervicis., Methods: We analyzed 30 consecutive patients who underwent C2-T1 PDF using an approach that preserved these three muscles without resecting. We assessed O-C2 range of motion (ROM), cross-sectional area of the cervical posterior muscles, rotational ROM, visual analog scale (VAS) for axial pain, neck disability index (NDI), and limitations of activities of daily living (ADL) involving neck movements., Results: Mean preoperative O-C2 ROM (23.6°) was significantly increased postoperatively (33.0°). Mean atrophy rate of the cross-sectional area was 3.9%. Postoperatively, 69.8% of the preoperative rotational ROM (113.3°) was retained. The preoperative VAS for axial pain and the NDI did not increase postoperatively. The postoperative O-C2 ROM (33.9°) in 26 patients for whom extension ADL were possible was significantly larger than that in four patients for whom extension ADL were impossible (26.9°). The postoperative retained rate of rotational ROM (75.8%) in 18 patients for whom rotation ADL were possible was significantly larger than that in 12 patients for whom rotation ADL were impossible (62.3%)., Conclusions: This is potentially an effective approach for maintaining O-C2 ROM and rotational ROM, which enabled good levels of ADL after C2-T1 PDF. Axial pain and NDI were not worse after PDF.

A 65-year-old man presented with gradually exacerbating low back pain. Magnetic resonance imaging revealed vertebral osteomyelitis in the Th11-L2 vertebral bodies and discs. The patient showed negative findings on conventional cultures. Direct broad-range polymerase chain reaction (PCR) with sequencing of the biopsied specimen had the highest similarity to the 16S rRNA gene of Helicobacter cinaedi. This case suggests that direct broad-range PCR with sequencing should be considered when conventional cultures cannot identify the causative organism of vertebral osteomyelitis, and that this method may be particularly useful when the pathogen is a fastidious organism, such as H. cinaedi.

A strain (Hime 5-1 T ) of lactic acid bacterium was isolated from the gut of the grasshopper Metrioptera engelhardti from a mountainous area of Nagano Prefecture, Japan. Strain Hime 5-1 T had a low 16S rRNA gene sequence similarity to known lactic acid bacteria, with the closest recognized relatives being Lactobacillus tucceti (96.7 %), Lactobacillus furfuricola (96.5 %), Lactobacillus versmoldensis (96.3 %) and Lactobacillus nodensis (96.1 %). Comparative analyses of the rpoA and pheS gene sequences indicated that Hime 5-1 T is not closely related to other Lactobacillus species. Strain Hime 5-1 T is a Gram-stain-positive, catalase-negative and homofermentative bacterium with yellowish colonies, which contrasts with the whitish colonies of its closest recognized relatives. Based on phenotypic and genotypic properties, we conclude that the isolated bacterium represents a novel species of the genus Lactobacillus, for which the name Lactobacillus metriopterae sp. nov. is proposed. The type strain is Hime 5-1 T (=JCM 31635 T =DSM 103730 T ). 16S rRNA gene based high-throughput sequencing revealed that L. metriopterae is the dominant microbiota in the gut of Metrioptera engelhardti.

Introduction: Difficulties with neck mobility often interfere with patients' activities of daily living (ADL) after cervical posterior spine surgery. The range of motion of the cervical spine decreases markedly after multilevel cervical posterior decompression and fusion (PDF). However, details regarding the limitations of cervical spine function due to postoperative reduced neck mobility after multilevel PDF are as yet unclarified. The present study aimed to clarify the quality of life and its related factors after PDF, and the optimal fixed neck position in multilevel PDF that minimizes the limitations of ADL accompanying markedly reduced postoperative neck mobility., Methods: Limitations of ADL involving neck extension, rotation, and flexion were investigated in 32 consecutive patients who underwent C2-T1 PDF using the responses to the cervical spine function domain of the Japanese Orthopedic Association Cervical Myelopathy Evaluation Questionnaire (JOACMEQ). The EuroQol 5 Dimension, Japanese Orthopedic Association score, and five domains of the JOACMEQ were also investigated. We investigated the risk factors regarding the fixed neck position in PDF for the impossibility to perform ADL involving each of three movements using cut-off values obtained from receiver-operating characteristic curves., Results: Postoperative comprehensive quality of life was significantly related to neurological improvements and to poor outcomes of cervical spine function after PDF. The significant risk factors for impossibility to perform ADL involving neck rotation were a C2-C7 lordotic angle ≥ 6° ( P = 0.0057) or a proportion coefficient of C2-T1 tilt angle/C2-C7 lordotic angle ≤ 1.8 ( P = 0.0024). There were no significant risk factors for impossibility to perform ADL involving neck extension or flexion., Conclusions: The optimal fixed neck position in C2-T1 PDF to reduce postoperative limitations of ADL involving neck mobility is a C2-C7 lordotic angle of less than 6°, or a C2-T1 tilt angle (°) of greater than 1.8 × the C2-C7 lordotic angle (°)., Competing Interests: Conflicts of Interest: The authors declare that there are no relevant conflicts of interest.

Background and Aim: Gastroesophageal reflux disease (GERD) and functional dyspepsia (FD) often coexist or overlap. In this study, the efficacy of acotiamide in combination with a standard dose of rabeprazole for GERD and FD was compared with that of a double dose of rabeprazole., Methods: Patients with overlap between GERD and FD experiencing heartburn and epigastric fullness symptoms after standard-dose proton pump inhibitor (PPI) for ≥ 8 weeks were randomized into two groups and received either acotiamide 300 mg/day + rabeprazole 10 mg/day or rabeprazole 20 mg/day for 4 weeks. Efficacy was assessed by reductions in symptom scores using the Izumo scale questionnaire and modified F-scale questionnaire., Results: As the primary endpoint, three upper gastrointestinal symptoms (heartburn, epigastralgia, and epigastric fullness) were reduced by ≥ 50% in 40.8% and 46.9% of patients in the combination and PPI double-dose groups, respectively, with no significant difference between the two groups. Essentially similar results were obtained for the modified F-scale questionnaire. No serious adverse events were noted., Conclusions: Acotiamide 300 mg/day in combination with rabeprazole 10 mg/day or rabeprazole 20 mg/day relieved symptoms in patients with overlap between GERD and FD experiencing heartburn and epigastric fullness symptoms after standard-dose PPI for ≥ 8 weeks, and the efficacies did not differ between the two treatments. The combination therapy may be an alternative option for persistent symptoms in these patients., (© 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

This study aimed to investigate the clinical outcomes of hematopoietic stem cell transplantation (HSCT) with total body irradiation-based myeloablative conditioning (TBI-MAC) in pediatric patients with acute lymphoblastic leukemia (ALL). We retrospectively examined patients with ALL who underwent HSCT with TBI-MAC from January 2000 to August 2016 at our institute. We enrolled 67 patients with a median follow-up period of 8 years. The 5-year event-free survival (EFS) and overall survival (OS) were 51.2% and 59.6%, respectively. At the first complete remission, HSCT exhibited significantly superior EFS and OS in our patients than that in patients with other diseases. We encountered 57.9% of patients with at least one late complication. Major late complications were short stature (26.3%) and hypogonadism (18.4%). While late complications were observed in several recipients of HSCT, late complication-related deaths occurred in three patients. The TBI-MAC regimen led to favorable clinical outcomes in pediatric patients with ALL who underwent HSCT. Thus, proper evaluation and management of late complications are mandatory.

Background: Six risk factors for screw cutout after internal fixation of intertrochanteric fractures have been reported. The purpose of the present study was to evaluate and compare the impact of the 6 risk factors of screw cutout to clarify the most important one., Methods: We enrolled 8 consecutive patients who had screw cutout and 48 random control subjects after internal fixation of intertrochanteric fractures treated with proximal femoral nail antirotation systems at our institution. All of the patients were female. The group that had screw cutout and the control group were retrospectively evaluated and compared with respect to the OTA/AO classification, presence of a posterolateral fragment, types of reduction pattern on anteroposterior and lateral radiographic images, position of the screw, and the presence of a tip-apex distance (TAD) of ≥20 mm. The impact of each factor on screw cutout was assessed using backward stepwise multivariable logistic regression analysis with the Akaike information criterion. Risk stratification was assessed using classification and regression tree (CART) analysis., Results: Among 6 risk factors, only a TAD of ≥20 mm had a significant impact on screw cutout, with an adjusted odds ratio of 12.4 (95% confidence interval, 1.6 to 129.0; p = 0.019). CART analysis also demonstrated that a TAD of ≥20 mm was the most important risk stratification factor (p < 0.001)., Conclusions: Among the 6 previously reported screw cutout-related factors, only a TAD of ≥20 mm was associated with screw cutout after internal fixation of intertrochanteric fractures with proximal femoral nail antirotation systems., Level of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Objective: Craniocervical junction arteriovenous fistulas(CCJ-AVFs)are extremely rare lesions that may result in both subarachnoid hemorrhage(SAH)and myelopathy. Diagnosis of CCJ-AVF is difficult and may be delayed due to variable clinical features and a spectrum of neuroradiological findings. To elucidate the clinical characteristics of CCJ-AVF, we analyzed the clinical symptoms, neuroimaging findings, and the results of surgical treatment in five patients., Results: Among the five patients, four were diagnosed with dural AVFs, and the remaining patient was diagnosed with radicular AVF. Two of the five patients presented with SAH, and the rest presented with myelopathy. In both the SAH patients, the initial digital subtraction angiography(DSA)failed to reveal the AVFs, and a definitive diagnosis was made only after repeated DSAs. In two of the three myelopathy patients, the diagnosis was delayed because of nonspecific chronic neurological symptoms which resembled a thoracolumbar lesion. Four patients underwent shunt occlusion through direct surgery and demonstrated favorable outcomes. One myelopathy patient, however, demonstrated abrupt onset, associated with progressive neurological deterioration, which resulted in poor prognosis. The magnetic resonance imaging(MRI)findings, which included intramedullary high intensity on a T2 weighted image, flow void, and varix at the cervical cord, were specific for the myelopathy patients., Conclusion: A thorough 4-vessel DSA study, including the cervical region, is mandatory for SAH patients whose clots are predominantly in the posterior fossa, and repeated DSA must be considered in cases of unknown origin. CCJ-AVF may cause myelopathy, with symptoms such as urinary dysfunction and/or paraparesis. Screening with a cervical MRI is useful for detecting CCJ-AVF in cases of myelopathy. Emergency radical treatment must be attempted for those patients demonstrating abrupt onset associated with symptoms of progressive deterioration, such as respiratory dysfunction or bulbar palsy.

Objectives: Ultraviolet (UV) light-mediated photofunctionalisation is known to improve osseointegration of pure titanium (Ti). However, histological examination of titanium alloy (Ti6Al4V), which is frequently applied in orthopaedic and dental surgery, has not yet been performed. This study examined the osseointegration of photofunctionalised Ti6Al4V implants., Methods: Ti and Ti6Al4V implants were treated with UV light, and the chemical composition and contact angle on the surfaces were evaluated to confirm photofunctionalisation. The implants were inserted into femurs in rats, and the rats were killed two or four weeks after the surgery. For histomorphometric analysis, both the bone-implant contact (BIC) ratio and the bone volume (BV) ratio were calculated from histological analysis and microcomputed tomography data., Results: The amount of carbon and the contact angle on both implants were significantly reduced after UV irradiation. The BIC ratios for both UV light-treated implants significantly increased at two weeks, but there was no significant difference at four weeks. There was no significant difference in the BV ratios between the UV light-treated and control implants at two or four weeks., Conclusions: This study suggests that photofunctionalisation of Ti6Al4V implants, similar to that of Ti implants, may promotes osseointegration in early but not in the late phase of osseointegration. Cite this article: R. Yamauchi, T. Itabashi, K. Wada, T. Tanaka, G. Kumagai, Y. Ishibashi. Photofunctionalised Ti6Al4V implants enhance early phase osseointegration. Bone Joint Res 2017;6:331-336. DOI: 10.1302/2046-3758.65.BJR-2016-0221.R1., Competing Interests: ICMJE Conflicts of Interest: None declared, (© 2017 Yamouchi et al.)

Collective behaviors of motile units through hydrodynamic interactions induce directed fluid flow on a larger length scale than individual units. In cells, active cytoskeletal systems composed of polar filaments and molecular motors drive fluid flow, a process known as cytoplasmic streaming. The motor-driven elongation of microtubule bundles generates turbulent-like flow in purified systems; however, it remains unclear whether and how microtubule bundles induce large-scale directed flow like the cytoplasmic streaming observed in cells. Here, we adopted Xenopus egg extracts as a model system of the cytoplasm and found that microtubule bundle elongation induces directed flow for which the length scale and timescale depend on the existence of geometrical constraints. At the lower activity of dynein, kinesins bundle and slide microtubules, organizing extensile microtubule bundles. In bulk extracts, the extensile bundles connected with each other and formed a random network, and vortex flows with a length scale comparable to the bundle length continually emerged and persisted for 1 min at multiple places. When the extracts were encapsulated in droplets, the extensile bundles pushed the droplet boundary. This pushing force initiated symmetry breaking of the randomly oriented bundle network, leading to bundles aligning into a rotating vortex structure. This vortex induced rotational cytoplasmic flows on the length scale and timescale that were 10- to 100-fold longer than the vortex flows emerging in bulk extracts. Our results suggest that microtubule systems use not only hydrodynamic interactions but also mechanical interactions to induce large-scale temporally stable cytoplasmic flow.

Objectives: The surface of pure titanium (Ti) shows decreased histocompatibility over time; this phenomenon is known as biological ageing. UV irradiation enables the reversal of biological ageing through photofunctionalisation, a physicochemical alteration of the titanium surface. Ti implants are sterilised by UV irradiation in dental surgery. However, orthopaedic biomaterials are usually composed of the alloy Ti6Al4V, for which the antibacterial effects of UV irradiation are unconfirmed. Here we evaluated the bactericidal and antimicrobial effects of treating Ti and Ti6Al4V with UV irradiation of a lower and briefer dose than previously reported, for applications in implant surgery., Materials and Methods: Ti and Ti6Al4V disks were prepared. To evaluate the bactericidal effect of UV irradiation, Staphylococcus aureus 834 suspension was seeded onto the disks, which were then exposed to UV light for 15 minutes at a dose of 9 J/cm 2 . To evaluate the antimicrobial activity of UV irradiation, bacterial suspensions were seeded onto the disks 0, 0.5, one, six, 24 and 48 hours, and three and seven days after UV irradiation as described above. In both experiments, the bacteria were then harvested, cultured, and the number of colonies were counted., Results: No colonies were observed when UV irradiation was performed after the bacteria were added to the disks. When the bacteria were seeded after UV irradiation, the amount of surviving bacteria on the Ti and Ti6Al4V disks decreased at 0 hours and then gradually increased. However, the antimicrobial activity was maintained for seven days after UV irradiation., Conclusion: Antimicrobial activity was induced for seven days after UV irradiation on both types of disk. Irradiated Ti6Al4V and Ti had similar antimicrobial properties. Cite this article: T. Itabashi, K. Narita, A. Ono, K. Wada, T. Tanaka, G. Kumagai, R. Yamauchi, A. Nakane, Y. Ishibashi. Bactericidal and antimicrobial effects of pure titanium and titanium alloy treated with short-term, low-energy UV irradiation. Bone Joint Res 2017;6:108-112. DOI: 10.1302/2046-3758.62.2000619., (© 2017 Itabashi et al.)

The metaphase spindle is organized for accurate chromosome segregation. One of the fundamental features of the spindle across the species is its symmetrical shape; the spindle consists of two polar arrays of microtubules at both ends. Although it has been suggested that the formation of the bipolar shape requires force balance coordination by molecular motors, i.e., kinesins and dyneins, quantitative analysis for the pole mechanics has not been conducted. Here, we demonstrate that it is not only the shape but also the stiffness and microtubule density of the pairs of pole regions are symmetrically balanced in single spindles self-assembled in Xenopus egg extracts. We found that the inhibition of dynein functions dramatically reduced the stiffness and microtubule density in the pole region. By contrast, the inhibition of one of the kinesins, Eg5, which is the antagonistic motor protein of dynein, increased the value of these parameters. Moreover, the inhibition of both dynein and Eg5 recovered these parameter values to those of non-treated spindle poles. We also found that, when one pole structure was held widened with the use of two glass microneedles, the opposite pole structure spontaneously widened, resulting in the formation of the barrel-like shaped spindle. The values of stiffness and microtubule density in the manipulated pole region decreased, following the spontaneous decrement of those in the paired unmanipulated pole region. These results suggest that the spindle possesses a mechanism to dynamically maintain its symmetry in mechanical properties., Competing Interests: Conflict of Interest The authors declare that they have no conflict of interest.

Background: Transplant recipients are supposedly in a more anemic, catabolic, and even inflammatory state at re-entering hemodialysis due to chronic rejection. The goal of this study was to clarify how transplant recipients can re-enter dialysis safely by focusing on control of anemia., Methods: From 2012 to 2014, a total of 29 transplant recipients re-entered hemodialysis because of chronic rejection (ie, the chronic kidney disease with transplant [CKDT] group). At the same time, in 2014, a total of 30 patients with chronic kidney disease without transplantation entered dialysis as the control group (ie, the CKD group). CKDT recipients (mean ± standard deviation age, 41.9 ± 11.8 years; 18 male subjects, 10 female subjects; frequency of diabetes, 10%; duration of graft survival, 12.5 ± 4.3 years) were younger and fewer had diabetes compared with the CKD group (age, 53.2 ± 10.5 years; 21 male subjects, 9 female subjects; frequency of diabetes, 36%). Patient characteristics at entering dialysis in both groups were analyzed according to retrospective chart review., Results: At entering dialysis, there were no significant differences between the CKD and CKDT groups in terms of the following: dose of darbepoetin; concentrations of hemoglobin, albumin, and C-reactive protein; cardiothoracic ratio; blood urea nitrogen and creatinine levels; estimated glomerular filtration rate; initial ultrafiltration; and duration of hospitalization for initiation of dialysis. The only difference between groups was mean weight at entry to dialysis (CKDT group, 58.5 ± 15.1 kg; CKD group, 67.1 ± 14.8 kg; P = .03). The darbepoetin dose per kilogram of weight did not differ between groups (CKDT, 2.28 ± 2.03 μg/kg; CKD, 2.12 ± 1.6 μg/kg; P = .95) in the final month before entry to dialysis., Conclusions: Safe re-initiation of dialysis is important for recipient survival. Although anemia is supposedly higher in transplant recipients due to immunosuppression, this single-center analysis found no difference in anemia in CKD with or without transplantation, caused by good use of erythropoietin-stimulating agents in both groups., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Study Design: Retrospective study comparing postoperative clinical outcomes after cervical laminoplasty between K-line (-) ossification of the posterior longitudinal ligament (OPLL) and K-line (+) OPLL in the neck-flexed position., Objective: To investigate postoperative outcomes using Japanese Orthopedic Association (JOA) scores, and grip-and-release (GR) and foot-tap (FT) test scores after laminoplasty in patients with K-line (-) OPLL in the neck-flexed position., Summary of Background Data: Cervical laminoplasty has been reported to lead to poor outcomes in K-line (-) OPLL and good outcomes in K-line (+) OPLL. The cervical spine, however, continues moving in the extension and flexion direction after laminoplasty., Methods: Patients with cervical myelopathy were divided into K-line (+) and (-) in the neck-flexed position. We compared postoperative outcomes after cervical laminoplasty using recovery rate, as assessed by the JOA score and degree of improvement in the six JOA score items, and performance, as assessed by GR and (FT) tests, between patients with K-line (+) OPLL (n = 18) and K-line (-) OPLL (n = 23) in the neck-flexed position., Results: Recovery rate of JOA score (23.8%) of patients in the K-line (-) group was significantly lower (P = 0.028) than that (46.3%) of K-line (+) group in the neck-flexed position. In the K-line (+) group, significant improvements were seen in all JOA-score items except bladder function; however, in the K-line (-) group, improvements were seen only in upper- and the lower-extremity sensory functions. In the K-line (+) group, mean GR and FT tests significantly improved, but in the K-line (-) group, only mean FT test significantly improved., Conclusion: The K-line (-) OPLL in the neck-flexed position is a risk factor for poor clinical outcome after cervical laminoplasty., Level of Evidence: 4.

Seven novel spiromeroterpenoids, asnovolins A-G (1-7), one of which was shown to suppress fibronectin expression, were isolated from Aspergillus novofumigatus CBS117520 along with a known compound, novofumigatonin (8). The structures of asnovolins A-G were elucidated using MS and 2D-NMR data. Asnovolin E (5) suppressed fibronectin expression by normal human neonatal dermal fibroblast cells.

Growth inhibitors were isolated from an arctic strain of Trichoderma polysporum, and the structures were elucidated and the in vitro inhibitory effects of these compounds against Pythium iwayamai were investigated. Eleven compounds were isolated; four showed a concentration-dependent growth-inhibitory effect against P. iwayamai. None of these compounds have been reported previously as substances with antimicrobial activity against P. iwayamai. One of these four compounds inhibited the growth of the pathogen at 33 μg ml(-1) concentration during a 15-day incubation at 20 °C. This effect was comparable to that of chloroneb (1: 1,4-dichloro-2,5-dimethoxybenzene), a fungicide with activity against P. iwayamai. Thus, the results of the present study show that the arctic strain of T. polysporum can be an effective source of antibiotics with activity against the snow rot pathogen, P. iwayamai.