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Soluble B-cell maturation antigen (sBCMA) is overexpressed on multiple myeloma (MM) cells. We investigated whether sBCMA levels correlated with other myeloma tumor volume indicators and its utility in monitoring oligo-secretory/non-secretory (O-S/Non-S) MM. In 115 patients with newly diagnosed MM, sBCMA was compared with M-protein levels, bone marrow plasma cells (BMPCs), circulating tumor cells (CTCs), and total diffusion volume (tDV; estimated by whole-body diffusion-weighted magnetic resonance imaging) at diagnosis. sBCMA levels increased significantly with International Staging System stage, chromosome 1q21 gain/amplification and CTC levels. sBCMA also correlated strongly with %BMPC (r = 0.65), moderately with tDV (r = 0.55) and paraprotein levels (involved immunoglobulin in IgG and IgA subtypes, r = 0.44 and 0.4; involved free light-chain levels in light-chain-only MM, r = 0.61, all P < 0.05). Longitudinal changes in sBCMA were consistent with disease status in both 17 O-S/Non-S and other secretory MM cases. Furthermore, sBCMA levels increased as early as 6 months pre-relapse in almost all O-S/Non-S relapsed patients. Thus, sBCMA correlates strongly with total tumor volume in MM, as assessed using different modalities. We suggest that sBCMA is useful, not only for monitoring responses in patients with O-S/Non-S MM but also for early relapse detection and prediction., (Copyright © 2024 American Society of Hematology.)

The persistent prevalence and dissemination of drug-resistant malaria parasites continue to challenge the progress of malaria eradication efforts. As a result, there is an urgent need to search for and develop innovative therapies. In this study, we screened synthetic 2,5-diphenyloxazole analogs from Oxytropis lanata. Among 48 compounds, 14 potently inhibited the proliferation of P. falciparum strains 3D7 (chloroquine-sensitive) and K1 (multidrug-resistant) in vitro, exhibited IC 50 values from 3.38 to 12.65 μM and 1.27-6.19 μM, respectively, and were toxic to human foreskin fibroblasts at 39.53-336.35 μM. Notably, Compounds 31 (2-(2',3'-dimethoxyphenyl)-5-(2″-hydroxyphenyl)oxazole) and 32 (2-(2',3'-dimethoxyphenyl)-5-(2″-benzyloxyphenyl)oxazole) exhibited the highest selectivity indices (SIs) against both P. falciparum strains (3D7/K1), with values > 40.20/>126.58 and > 41.27/> 59.06, respectively. In the IC 50 speed and stage-specific assays, Compounds 31 and 32 showed slow action, along with distinct effects on the ring and trophozoite stages. Microscopy observations further revealed that both compounds impact the development and delay the progression of the trophozoite and schizont stages in P. falciparum 3D7, especially at concentrations 100 times their IC 50 values. In a 72-h in vitro exposure experiment at their respective IC 80 in P. falciparum 3D7, significant alterations in parasitemia levels were observed compared to the untreated group. In Compound 31-treated cultures, parasites shrank and were unable to reinvade red blood cells (RBCs) during an extended 144-h incubation period, even after compound removal from the culture. In vivo assessments were conducted on P. yoelii 17XNL-infected mice treated with Compounds 31 and 32 at 20 mg/kg administered once daily for ten days. The treated groups showed statistically significant lower peaks of parasitemia (Compound 31-treated: trial 1 12.7%, trial 2 15.8%; Compound 32-treated: trial 1 12.7%, trial 2 14.0%) compared to the untreated group (trial 1 21.7%, trial 2 28.3%). These results emphasize the potential of further developing 2,5-diphenyloxazoles as promising antimalarial agents., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The incidence of rod fracture after corrective surgery for adult spinal deformity (ASD) is high. Although many reports have investigated the effects of rod bending considering postoperative body motion, and countermeasures, there are no reports investigating the effects during intraoperative correction. The purpose of this study was to investigate the effect of ASD correction on rods by using finite element analysis (FEA) based on the rod shape changes before and after spinal corrective fusion., Methods: Five ASD patients (mean age 73 years, all female) who underwent thoracic to pelvic fusion were included in this study. A 3D rod model was created using computer-aided design software from digital images of the intraoperatively bended rod and intraoperative X-ray images after corrective fusion. The 3D model of the bent rod was meshed by dividing each of the screw head intervals into 20 sections and cross-section of the rod into 48 sections. Two surgical fusion methods of stepwise fixation as the cantilever method and parallel fixation as the translational method were simulated to evaluate stress and bending moments on the rods during intraoperative correction., Results: The stresses on the rods were 1500, 970, 930, 744, and 606 MPa in the five cases for stepwise fixation and 990, 660, 490, 508, and 437 MPa for parallel fixation, respectively, with parallel fixation having lower stresses in all cases. In all cases, maximum stress was found around the apex of the lumbar lordosis and near L5/S1. The bending moment was high around L2-4 in most cases., Conclusions: The external forces of intraoperative correction had the greatest effect on the lower lumbar region, especially around the apex of the lumbar lordosis., Competing Interests: Declaration of competing interest All authors declare that there are no other conflicts of interest., (Copyright © 2023 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Anorexia is a behavioral change caused by functional brain disorders in patients with Alzheimer's disease (AD). Amyloid-β (1-42) oligomers (o-Aβ) are possible causative agents of AD that impair signaling via synaptic dysfunction. In this study, we used Aplysia kurodai to study functional disorders of the brain through o-Aβ. Administration of o-Aβ to the buccal ganglia (feeding brain for oral movements) by surgical treatment significantly reduced food intake for at least five days. Furthermore, we explored the effects of o-Aβ on the synaptic function in the feeding neural circuit, focusing on a specific inhibitory synaptic response in jaw-closing motor neurons produced by cholinergic buccal multi-action neurons because we recently found that this cholinergic response decreases with aging, which is consistent with the cholinergic hypothesis for aging. Administration of o-Aβ to the buccal ganglia significantly reduced the synaptic response within minutes, whereas administration of amyloid-β (1-42) monomers did not. These results suggest that o-Aβ may impair the cholinergic synapses, even in Aplysia, which is consistent with the cholinergic hypothesis for AD., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Laparoscopic (lap) colectomies for advanced colorectal cancer (CRC) often require resection of other organs. We systematically reviewed currently available literature on lap multi-visceral resection for CRC, with regard to short- and long-term oncological outcomes, and compared them with open procedures. We performed a systematic literature search in MEDLINE, EMBASE, Google Scholar and PubMed from inception to November 30, 2020. The aim of this study was to synthesize short-term and oncological outcomes associated with laparoscopic versus open surgery. Pooled proportions and risk ratios (RRs) were calculated using an inverse variance method. We included six observational cohort studies published between 2012 and 2020 (lap procedures: n = 262; open procedures: n = 273). Collectively, they indicated that postoperative complications were significantly more common after open surgeries than lap surgeries (RR: 0.53; 95% confidence interval [CI]: 0.39-0.72; P < 0.00001), but the two approaches did not significantly differ in positive resection margins (RR: 0.75; 95% CI: 0.38-1.50; P = 0.42), local recurrence (RR: 0.66; 95% CI: 0.28-1.62; P = 0.37), or (based on two evaluable studies) 5-year OS (RR: 0.70; 95% CI: 0.46-1.04; P = 0.08) or 5-year DFS (RR: 0.86; 95% CI: 0.67-1.11) for T4b disease. In conclusion, laparoscopic and open multi-visceral resections for advanced CRC have comparable oncologic outcomes. Although a randomized study would be ideal for further research, no such studies are currently available., Competing Interests: Declaration of competing interest Drs Y Ishiyama, Y Tachimori, I Mochizuki, Y Tomozawa, S Ito, M Oneyama, M Amiki, Y Hara, K Narita, M Goto, K Sekikawa, and Y Hirano have no conflicts of interest or financial ties to disclose., (Copyright © 2022 Asian Surgical Association and Taiwan Robotic Surgery Association. Published by Elsevier B.V. All rights reserved.)

Angioimmunoblastic T-cell lymphoma (AITL) is proposed to be initiated by age-related clonal hematopoiesis (ACH) with TET2 mutations, whereas the G17V RHOA mutation in immature cells with TET2 mutations promotes the development of T follicular helper (TFH)-like tumor cells. Here, we investigated the mechanism by which TET2-mutant immune cells enable AITL development using mouse models and human samples. Among the 2 mouse models, mice lacking Tet2 in all the blood cells (Mx-Cre × Tet2flox/flox × G17V RHOA transgenic mice) spontaneously developed AITL for approximately up to a year, while mice lacking Tet2 only in the T cells (Cd4-Cre × Tet2flox/flox × G17V RHOA transgenic mice) did not. Therefore, Tet2-deficient immune cells function as a niche for AITL development. Single-cell RNA-sequencing (scRNA-seq) of &gt;50 000 cells from mouse and human AITL samples revealed significant expansion of aberrant B cells, exhibiting properties of activating light zone (LZ)-like and proliferative dark zone (DZ)-like germinal center B (GCB) cells. The GCB cells in AITL clonally evolved with recurrent mutations in genes related to core histones. In silico network analysis using scRNA-seq data identified Cd40-Cd40lg as a possible mediator of GCB and tumor cell cluster interactions. Treatment of AITL model mice with anti-Cd40lg inhibitory antibody prolonged survival. The genes expressed in aberrantly expanded GCB cells in murine tumors were also broadly expressed in the B-lineage cells of TET2-mutant human AITL. Therefore, ACH-derived GCB cells could undergo independent clonal evolution and support the tumorigenesis in AITL via the CD40-CD40LG axis., (© 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Several risk scoring and ranking methods have been applied for the prioritization of micropollutants, including pesticides, and in the selection of pesticides to be regulated regionally and nationally. However, the effectiveness of these methods has not been evaluated in Japan. We developed a risk prediction method to select pesticides that have a high probability of being detected in drinking water sources where no monitoring data is available. The risk prediction method was used to select new pesticides for the 2013 Primary List in the Japanese Drinking Water Quality Guidelines. Here, we examined the effectiveness of the method on the basis of the results of water quality examinations conducted by water supply authorities across Japan, and studied ways to improve the risk prediction method. Of the 120 pesticides in the 2013 Primary List, 80 were detected in drinking water sources (raw water entering water treatment plants). The rates of detection of the newly selected pesticides and previously listed pesticides were not significantly different: 64% and 68%, respectively. When the risk predictor was revised to incorporate degradability of dry-field pesticides and current pesticide sales data, the rate of detection of pesticides selected as having a high risk of detection improved from 72% to 88%. We prepared regional versions of the Primary List using the revised risk predictors and verified their utility. The number of listed pesticides varied greatly by region, ranging from 32 to 73; all regional lists were much shorter than the national Primary List. In addition, 55% to 100% of the pesticides detected in each region were included in a Regional Primary List. This work verifies the ability of the risk prediction method to screen pesticides and select those with a high risk of detection., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Electroconvulsive therapy (ECT) is effective for treating depression. However, the mechanisms underlying the antidepressant effects of ECT remain unknown. Depressed patients exhibit abnormal Ca 2+ kinetics. Early stages of the intracellular Ca 2+ signaling pathway involve the release of Ca 2+ from the endoplasmic reticulum (ER) via Ca 2+ release channels., Objective: We considered that depression may be improved via ECT-induced normalization of intracellular Ca 2+ regulation through the Ca 2+ release channels. The current study aimed to investigate the effects of ECT on two Ca 2+ release channels, ryanodine receptors (RyRs) and inositol 1,4,5-trisphosphate receptors (IP 3 Rs)., Methods: A mouse depression-like model subjected to water immersion with restraint stress was administered electroconvulsive shock (ECS) therapy. Their depression-like status was behaviorally and histologically assessed using forced swimming tests, novelty-suppressed feeding tests, and by evaluating neurogenesis in the hippocampal dentate gyrus, respectively. A RyRs blocker, dantrolene, was administered prior to ECS, and the changes in depression-like conditions were examined., Results: The protein expressions of RyR1 and RyR3 significantly increased in the hippocampus of the mouse model with depression-like symptoms. This increase was attenuated as depression-like symptoms were reduced due to ECS application. However, pre-injection with dantrolene reduced the antidepressant effects of ECS., Conclusions: A significant increase in RyRs expression in a depression-like state and exacerbation of depression-like symptoms by RyRs inhibitors may be caused by RyRs dysfunction, suggesting overexpression of RyRs is a compensatory effect. Normalization of RyRs expression levels by ECS suggests that ECT normalizes the Ca 2+ release via RyRs. Thus, normalizing the function of RyRs may play an important role in the therapeutic effect of ECT., Competing Interests: Declaration of competing interest None., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Hydroxylation activity at the 6β-position of steroid hormones (testosterone, progesterone, and cortisol) by human cytochromes P450 (CYP) 3A4, polymorphic CYP3A5, and fetal CYP3A7 were compared to understand the catalytic properties of the major forms of human CYP3A subfamily. Testosterone, progesterone, and cortisol 6β-hydroxylation activities of recombinant CYP3A4, CYP3A5, and CYP3A7 were determined by liquid chromatography. Michaelis constants (K m ) for CYP3A7-mediated 6β-hydroxylation of testosterone, progesterone, and cortisol were similar to those of CYP3A4 and CYP3A5. The maximal velocity (k cat ) and k cat /K m values for CYP3A4 were the highest, followed by CYP3A5 and those for CYP3A7 were the lowest among three CYP3A subfamily members. A decrease in K m values for progesterone 6β-hydroxylation by CYP3A4, CYP3A5, and CYP3A7 in the presence of testosterone was observed, and the k cat values for CYP3A5 gradually increased with increasing testosterone. This indicated that testosterone stimulated progesterone 6β-hydroxylation by all three CYP3A subfamily members. However, progesterone inhibited testosterone 6β-hydroxylation mediated by CYP3A4, CYP3A5, and CYP3A7. In conclusion, the k cat values, rather than K m values, for 6β-hydroxylation of three steroid hormones mediated by CYP3A7 were different from those for CYP3A4 and CYP3A5. In addition, the inhibitory/stimulatory pattern of steroid-steroid interactions would be different among CYP3A subfamily members., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Suicide is a major cause of death among inpatients with schizophrenia. However, there are only a limited number of surveys of suicide among such patients, especially in Asia. Therefore, we conducted a multi-institutional survey on suicide death among inpatients with schizophrenia in Japan. We investigated the characteristics of patients with schizophrenia who died by suicide during hospitalization in psychiatric wards, and simultaneously, those of patients with depression. Forty-five suicides of patients with schizophrenia occurred in 27 hospitals, and 46 suicides of patients with depression occurred in 33 hospitals. Hanging was the most common suicide method in both diagnostic groups. More than half of the patients with schizophrenia had histories of suicide attempts, although there was no significant difference in previous suicide attempts or self-harm between both diagnostic groups. Medical staff should confirm whether inpatients with schizophrenia have such histories. In this study, there was no significant difference in characteristics between inpatients with schizophrenia or depression. In order to prevent suicides of patients with schizophrenia during hospitalization, nonspecific suicide attempt prevention needs to be undertaken, such as ensuring comprehension of the general risk factors of suicide among medical staff., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interests., (Copyright © 2019. Published by Elsevier B.V.)

Background: Mycoplasma pneumoniae pneumonia (MPP) is generally a self-limiting disease, but it may become refractory. It is thought that refractory MPP is linked to the excessive immunologic responses of the host. Consequently, the use of adjunctive systemic corticosteroids may have beneficial effects. In this study, we compared the effects of high- and low-dose corticosteroid therapy in a pediatric population with refractory MPP., Methods: We retrospectively collected data from 91 pediatric MPP patients treated with adjunctive systemic corticosteroids between April 2014 and October 2016. The patients were divided into the following two groups: high-dose corticosteroid group (2 mg/kg/day or more of prednisolone equivalents; n = 38) and low-dose corticosteroid group (<2 mg/kg/day; n = 53). Additionally, we compared the number of febrile days post-corticosteroid administration. We used 25 paired patients in a propensity score matching analysis to correct for confounding factors both by age and by days (from onset till corticosteroid therapy initiation)., Results: We observed that in the high-dose corticosteroid group defervescence following corticosteroid therapy initiation was achieved significantly earlier and length of hospitalization was significantly shorter (0.8 ± 1.0 vs. 1.5 ± 1.4 days and 8.2 ± 2.4 vs. 10.7 ± 2.7 days, respectively). In the propensity score matching, we observed that significant differences in the length of fever following corticosteroid therapy initiation and hospitalization were still present. Further, neither of the groups developed corticosteroid-related adverse events., Conclusion: Our results suggest that patients with refractory MPP treated with high-dose corticosteroid could achieve defervescence earlier and have a shorter hospitalization., (Copyright © 2019 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Objective: Arima syndrome (AS) is a rare disease and its clinical features mimic those of Joubert syndrome or Joubert syndrome-related diseases (JSRD). Recently, we clarified the AS diagnostic criteria and its severe phenotype. However, genetic evidence of AS remains unknown. We explored causative genes of AS and compared the clinical and genetic features of AS with the other JSRD., Patients and Methods: We performed genetic analyses of 4 AS patients of 3 families with combination of whole-exome sequencing and Sanger sequencing. Furthermore, we studied cell biology with the cultured fibroblasts of 3 AS patients., Results: All patients had a specific homozygous variant (c.6012-12T>A, p.Arg2004Serfs*7) or compound heterozygous variants (c.1711+1G>A; c.6012-12T>A, p.Gly570Aspfs*19;Arg2004Serfs*7) in centrosomal protein 290 kDa (CEP290) gene. These unique variants lead to abnormal splicing and premature termination. Morphological analysis of cultured fibroblasts from AS patients revealed a marked decrease of the CEP290-positive cell number with significantly longer cilium and naked and protruded ciliary axoneme without ciliary membrane into the cytoplasm., Conclusion: AS resulted in cilia dysfunction from centrosome disruption. The unique variant of CEP290 could be strongly linked to AS pathology. Here, we provided AS specific genetic evidence, which steers the structure and functions of centrosome that is responsible for normal ciliogenesis. This is the first report that has demonstrated the molecular basis of Arima syndrome., (Copyright © 2017 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Background: Patients with involutional blepharoptosis sometimes require reoperation because of functional or esthetic reasons after the primary operation. Few studies have analyzed the risk factors for reoperation in such cases., Methods: We retrospectively analyzed the cases of 274 patients who underwent levator aponeurosis surgery for bilateral involutional blepharoptosis. We examined the risk factors for reoperation using univariate and multivariate analyses., Results: Reoperation was performed for 89 of the 274 patients (32.5%). There was no significant difference in the rate of reoperation among surgeons. In the univariate analysis, patients with preoperative asymmetry, defined as a difference of >1 mm in the marginal reflex distance between the right and left sides, showed a significantly higher rate of reoperation (42.7%) than those without asymmetry (28.1%) (p = 0.018). Age, sex, and ptosis severity did not affect the rate of reoperation. The multivariate analysis with a logistic regression showed that preoperative asymmetry was a significant risk factor for reoperation, with an odds ratio of 1.90 (p = 0.019)., Conclusion: In involutional blepharoptosis, patients with preoperative asymmetry should be informed of the higher risk of reoperation, and the balance between the right and left sides should be carefully adjusted intraoperatively., (Copyright © 2017 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

We report an immunocompromised child who experienced two episodes of bacteremia due to Streptococcus pyogenes. Random amplification of polymorphic DNA profiles, emm genotypes, superantigen profiles, antimicrobial susceptibility, and resistance-related genes were investigated, and the results showed different profiles between the two isolates. This is the first report describing recurrent bacteremia caused by different strains of S. pyogenes., (Copyright © 2016 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

In previous studies, it has been concluded that volume losses (V loss) of the Ti-29Nb-13Ta-4.6Zr (TNTZ) discs and balls are larger than those of the respective Ti-6Al-4V extra-low interstitial (Ti64) discs and balls, both in air and Ringer's solution. These results are related to severe subsurface deformation of TNTZ, which is caused by the lower resistance to plastic shearing of TNTZ than that of Ti64. Therefore, it is necessary to further increase the wear resistance of TNTZ to satisfy the requirements as a biomedical implant. From this viewpoint, interstitial oxygen was added to TNTZ to improve the plastic shear resistance via solid-solution strengthening. Thus, the wear behaviors of combinations comprised of a new titanium alloy, TNTZ with high oxygen content of 0.89 mass% (89O) and a conventional titanium alloy, Ti64 were investigated in air and Ringer's solution for biomedical implant applications. The worn surfaces, wear debris, and subsurface damage were analyzed using a scanning electron microscopy and an electron probe microanalysis. V loss of the 89O discs and balls are smaller than those of the respective TNTZ discs and balls in both air and Ringer's solution. It can be concluded that the solid-solution strengthening by oxygen effectively improves the wear resistance for TNTZ materials. However, the 89O disc/ball combination still exhibits higher V loss than the Ti64 disc/ball combination in both air and Ringer's solution. Moreover, V loss of the disc for the 89O disc/Ti64 ball combination significantly decreases in Ringer's solution compared to that in air. This decrease for the 89O disc/Ti64 ball combination in Ringer's solution can be explained by the transition in the wear mechanism from severe delamination wear to abrasive wear., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

In this study, various amounts of oxygen were added to Ti-10Cr (mass%) alloys. It is expected that a large changeable Young's modulus, caused by a deformation-induced ω-phase transformation, can be achieved in Ti-10Cr-O alloys by the appropriate oxygen addition. This "changeable Young's modulus" property can satisfy the otherwise conflicting requirements for use in spinal implant rods: high and low moduli are preferred by surgeons and patients, respectively. The influence of oxygen on the microstructures and mechanical properties of the alloys was examined, as well as the bending springback and cytocompatibility of the optimized alloy. Among the Ti-10Cr-O alloys, Ti-10Cr-0.2O (mass%) alloy shows the largest changeable Young's modulus following cold rolling for a constant reduction ratio. This is the result of two competing factors: increased apparent β-lattice stability and decreased amounts of athermal ω phase, both of which are caused by oxygen addition. The most favorable balance of these factors for the deformation-induced ω-phase transformation occurred at an oxygen concentration of 0.2mass%. Ti-10Cr-0.2O alloy not only exhibits high tensile strength and acceptable elongation, but also possesses a good combination of high bending strength, acceptable bending springback and great cytocompatibility. Therefore, Ti-10Cr-0.2O alloy is a potential material for use in spinal fixture devices., (Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

The predominant factor determining the wear properties of a new titanium alloy, Ti-29Nb-13Ta-4.6Zr (TNTZ) and a conventional titanium alloy, Ti-6Al-4V extra-low interstitial (Ti64) was investigated for TNTZ and Ti64 combinations in metal-to-metal contacting bio-implant applications. The worn surfaces, wear debris, and subsurface damages were analyzed using a scanning electron microscopy combined with energy-dispersive spectroscopy and electron-back scattered diffraction analysis. The volume loss of TNTZ is found to be larger than that of Ti64, regardless of the mating material. The wear track of TNTZ exhibits the galled regions and severe plastic deformation with large flake-like debris, indicative of delamination wear, which strongly suggests the occurrence of adhesive wear. Whereas, the wear track of Ti64 have a large number of regular grooves and microcuttings with cutting chip-like wear debris and microfragmentation of fine oxide debris, indicative of abrasive wear combined with oxidative wear. This difference in the wear type is caused by severe and mild subsurface deformations of TNTZ and Ti64, respectively. The lower resistance to plastic shearing for TNTZ compared to that of Ti64 induces delamination, resulting in a higher wear rate., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Spiruchostatin A (SP-A) and spiruchostatin B (SP-B) are the potent histone deacetylase inhibitors (HDACi), that has the potential for chemotherapy of leukemia but the exact mechanism of these compounds remains unclear. In the present study, the role of reactive oxygen species (ROS) production and the mechanism involved in the apoptosis was investigated in human lymphoma U937 cell. When the U937 cells were treated with SP-A and SP-B for 24h at different concentrations, evidence of apoptotic features, including increase in DNA fragmentation and changes in nuclear morphology, were obtained. SP-B showed maximum potency to induce apoptosis, while SP-A was less potent. Apoptosis was also determined by increase in the fraction of sub-G1 cells and Annexin V-FITC staining cells. SP-A and SP-B induced apoptosis was accompanied by significant increase in the formation of intracellular reactive oxygen species (ROS). Pre-treatment with N-acetyl-l-cysteine (NAC), significantly inhibited the SP-A and SP-B mediated apoptosis, suggesting a vital role of ROS involved in the lethality of both agents. Moreover, SP-A and SP-B treatment resulted in the loss of mitochondrial membrane potential (MMP), and Fas, caspase-8 and caspase-3 activation. In addition Bid activation and the release of cytochrome-c to the cytosol was also observed. In this study, we suggest that a marked induction of intracellular ROS mediated mitochondrial pathway and the Fas plays a role in the SP-A and SP-B induced apoptosis. Taken together, our data provides further insights of the mechanism of action of SP-A and SP-B and their potential application as novel chemotherapeutic agents., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Some newly developed β-type titanium alloys for biomedical applications exhibit distinctive heterogeneous structures. The formation mechanisms for these structures have not been completely revealed; however, understanding these mechanisms could lead to improving their properties. In this study, the heterogeneous structures of a Ti-29Nb-13Ta-4.6Zr alloy (TNTZ), which is a candidate for next-generation metallic biomaterials, were analyzed. Furthermore, the effects of such heterogeneous structures on the mechanical strength of this alloy, including fatigue strength, were revealed by comparing its strength to that of homogenous TNTZ. The heterogeneous structures were characterized micro-, submicro- and nano-scale wave-like structures. The formation mechanisms of these wave-like structures are found to be different from each other even though their morphologies are similar. It is revealed that the micro-, submicro- and nano-scale wave-like structures are caused by elemental segregation, crystal distortion related to kink band and phase separation into β and β', respectively. However, these structures have no significant effect on both tensile properties and fatigue strength comparison with homogeneous structure in this study., (© 2013 Published by Elsevier Ltd.)

The mechanical strength of a beta titanium alloy such as Ti-Nb-Ta-Zr alloy (TNTZ) can be improved significantly by thermo-mechanical treatment. In this study, TNTZ was subjected to solution treatment, cold caliber rolling, and cold swaging before aging treatment to form a rod for spinal fixation. The {110}(β) are aligned parallel to the cross-section with two strong peaks approximately 180° apart, facing one another, in the TNTZ rods subjected to cold caliber rolling and six strong peaks at approximately 60° intervals, facing one another, in the TNTZ rods subjected to cold swaging. Therefore, the TNTZ rods subjected to cold swaging have a more uniform structure than those subjected to cold caliber rolling. The orientation relationship between the α and β phases is different. A [110](β)//[121](α), (112)(β)//(210)(α) orientation relationship is observed in the TNTZ rods subjected to aging treatment at 723 K after solution treatment and cold caliber rolling. On the other hand, a [110](β)//[001](α), (112)(β)//(200)(α) orientation relationship is observed in TNTZ rod subjected to aging treatment at 723 K after cold swaging. A high 0.2% proof stress of about 1200 MPa, high elongation of 18%, and high fatigue strength of 950 MPa indicate that aging treatment at 723 K after cold swaging is the optimal thermo-mechanical process for a TNTZ rod., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

In this review, we propose a new classification of vertebrate cilia/flagella and discuss the evolution and prototype of cilia. Cilia/flagella are evolutionarily well-conserved membranous organelles in eukaryotes and serve a variety of functions, including motility and sensation. Vertebrate cilia have been traditionally classified into conventional motile cilia and sensory primary cilia. However, an avalanche of emerging evidence on the variations of cilia has made it almost impossible to classify them in a simple dichotomic manner. For example, conventional motile cilia are also involved in the sensation of bitter taste to facilitate the beating of cilia as a defense system of the respiratory system. On the other hand, the primary cilium, often regarded as a non-motile sensory organelle, has been revealed to be motile in vertebrate embryonic nodes, where they play a crucial role in the determination of left-right asymmetry of the body. Moreover, choroid plexus epithelial cells in the cerebral ventricular system exhibit multiple primary cilia on a single cell. Considering these lines of evidence on the diversity of cilia, we believe the classification of cilia should be based on their structure and function, and include more detailed criteria. Another intriguing issue is how in the evolution of cilia, their function and morphology are combined. For example, has motility been acquired from originally sensory cilia, or vice versa? Alternatively, were they originally hybrid in nature? These questions are inseparable from the classification of cilia per se. We would like to address these conundrums in this review article, principally from the standpoint of differentiation of the animal cell., (Copyright © 2011 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.)

Purpose: Atherosclerosis is thought to be initiated by the transendothelial migration of monocytes. In the early stage of this process, the adhesion of monocytes to endothelial cells is supported by an increase in the intracellular concentration of calcium ion ([Ca(2+)]i) in endothelial cells. However, the main source of Ca(2+) has been unclear. In this study, the changes in ionic transmittance and [Ca(2+)]i due to the adhesion of monocytes were continuously measured by an electrophysiological technique and fluorescent imaging. Especially, we focused on transient receptor potential vanilloid channel 1 (TRPV1) as a Ca(2+) channel that could influence the adhesion of monocytes., Material and Methods: Whole-cell current was continuously recorded in human umbilical vein endothelial cells (HUVECs) by a patch electrode., Results: The adhesion of monocytes (THP-1) induced a transient inward current in HUVECs, as well as an elevation of [Ca(2+)]i. This inward element was abolished by the application of 100 nM SB366,791, a selective antagonist of TRPV1 channel. Furthermore, SB366,791 significantly decreased the number of THP-1 cells that adhered to HUVECs (control: 231 ± 38, SB366,791: 96 ± 16 cells/mm2)., Conclusion: These results suggest that an inward calcium current via the TRPV1 channels of endothelial cells correlates with a stronger adhesion between monocytes and endothelial cells.

Interspecies somatic cell nucleus transfer (iSCNT) could be a useful bioassay system for assessing the ability of mammalian somatic cells to develop into embryos. To examine this possibility, we performed canine iSCNT using porcine oocytes, allowed to mature in vitro, as recipients. Canine fibroblasts from the tail tips and dewclaws of a female poodle (Fp) and a male poodle (Mp) were used as donors. We demonstrated that the use of porcine oocytes induced blastocyst formation in the iSCNT embryos cultured in porcine zygote medium-3. In Fp and Mp, the rate of blastocyst formation from cleaved embryos (Fp: 6.3% vs. 22.4%; and Mp: 26.1% vs. 52.4%) and the number of cells at the blastocyst stage (Fp: 30.7 vs. 60.0; and Mp: 27.2 vs. 40.1) were higher in the embryos derived from dewclaw cells than in those derived from tail-tip cells (P<0.05). The use of donor cells of any type in later passages decreased the rate of blastocyst formation. Treatment with trichostatin-A did not improve the rate of blastocyst formation from cleaved dewclaw cell-derived embryos but did so in the embryos derived from the tail-tip cells of Fp. Only blastocysts derived from dewclaw cells of Mp developed outgrowths. However, outgrowth formation was retrieved in the embryos derived from dewclaw cells of Fp by aggregation at the 4-cell stage. We inferred that iSCNT performed using porcine oocytes as recipients could represent a novel bioassay system for evaluating the developmental competence of canine somatic cells.

Background: Recent accumulating lines of evidence reveal that leptin is associated with synaptic plasticity and neuroprotective activity in the brain., Methods: In this preliminary study with a cross-sectional design, we examined the relationship between plasma leptin level and total or regional gray matter (GM) volume in 34 elderly subjects (mean age 64.5 years) with normal fasting glucose level and without dementia and metabolic syndrome by voxel-based morphometry of magnetic resonance imaging scans., Results: Plasma leptin level showed no significant correlation with total GM volume but showed a significantly positive correlation with GM volumes in the right hippocampus, left parahippocampus, and right cerebellum with adjustments for age, gender, body mass index (BMI), and waist-to-hip ratio (W/H). Also, after adjustments for age, gender, BMI, W/H, and intracranial volume, plasma leptin level significantly positively correlated with GM volumes in the right hippocampus and bilateral cerebella but not with that in the left parahippocampus., Conclusions: The results of this pilot study would be beneficial for our understanding of the neuroprotective effects of leptin on human brain aging.

Objective: To compare postcontrast T1-weighted imaging (T1WI+) with precontrast T1-weighted (T1WI-), T2-weighted (T2WI), and proton density-weighted imaging (ProWI) in depiction of the anterior disc displacement (ADD) in temporomandibular disorders (TMDs)., Study Design: A total of 120 joints with TMD were included in this study. Qualitatively, Receiver operating characteristic analysis was performed. Quantitatively, the ratio of the intensity in the retrodiscal tissue to intensity in the disc (intensity ratio) was measured., Results: One reader achieved superior performance in visualization of ADD with T1WI+ than with the other sequences. The other reader showed superiority with T1WI+ rather than T2WI or T1WI-. The intensity ratio on T1WI+ was significantly higher than the intensity ratio on other sequences. On T1WI,+ the intensity ratio in the joints with ADD was significantly higher than that in the joints without ADD., Conclusion: Postcontrast T1-weighted imaging can improve the visualization of ADD in TMDs.

Staphylococcus aureus expresses a repertoire of factors including staphylococcal exotoxins (SEs), exoenzymes, and numerous cell-associated components that contribute to the pathogenesis of disease. We constructed and expressed a nontoxic double mutant SEC (dmSEC), devoid of superantigenic activity, and investigated the ability of intranasal vaccination with dmSEC plus cholera toxin (CT) adjuvant to protect mice against S. aureus infection. Mice were vaccinated with dmSEC and inoculated with a viable S. aureus clinical isolate strain. The survival rate in the immunized mice was higher, and bacterial counts in the organs were significantly lower than those in the control group. Intranasal vaccination with dmSEC induced the production of SEC-specific antibodies such as IgG1, IgG2b and IgA. dmSEC-vaccinated mice elicited significantly higher titers of interleukin-4 (IL-4) and IL-10, and lower levels of interferon-gamma (IFN-gamma) after challenge with S. aureus compared with the control group. Furthermore, the sera from dmSEC-immunized mice significantly inhibited IFN-gamma and tumor necrosis factor-alpha production in vitro. These results indicate that intranasal vaccination with dmSEC devoid of superantigenic properties induces systemic immune responses and provides protection against S. aureus infection.

Ca(2+)-induced Ca2+ release (CICR) occurs in frog motor nerve terminals after ryanodine receptors (RyRs) are primed for activation by conditioning large Ca2+ entry. We studied which type of RyR exists, whether CICR occurs without conditioning Ca2+ entry and how RyRs are primed. Immunohistochemistry revealed the existence of RyR3 in motor nerve terminals and axons and both RyR1 and RyR3 in muscle fibers. A blocker of RyR, 8-(N,N-diethylamino)octyl 3,4,5-trimethoxybenzoate hydrochloride (TMB-8) slightly decreased rises in intracellular Ca2+ ([Ca2+]i) induced by a short tetanus (50 Hz, 1-2s), but not after treatment with ryanodine. Repetitive tetani (50 Hz for 15s every 20s) produced repetitive rises in [Ca2+]i, whose amplitude overall waxed and waned. TMB-8 blocked the waxing and waning components. Ryanodine suppressed a slow increase in end-plate potentials (EPPs) induced by stimuli (33.3 Hz, 15s) in a low Ca2+, high Mg2+ solution. KN-62, a blocker of Ca(2+)/calmoduline-activated protein kinase II (CaMKII), slightly reduced short tetanus-induced rises in [Ca2+]i, but markedly the slow waxing and waning rises produced by repetitive tetani in both normal and low Ca2+, high Mg2+ solutions. Likewise, KN-62, but not KN-04, an inactive analog, suppressed slow increases in EPP amplitude and miniature EPP frequency during long tetanus. Thus, CICR normally occurs weakly via RyR3 activation by single impulse-induced Ca2+ entry in frog motor nerve terminals and greatly after the priming of RyR via CaMKII activation by conditioning Ca2+ entry, thus, facilitating transmitter exocytosis and its plasticity.

Little data is available recommending the adequate exercise level for physical fitness, so we hypothesized that the anaerobic threshold (AT) point is an ideal exercise level. We aimed to determine a new target heart rate formula for the adequate exercise training level in healthy subjects. This study first developed a new formula in 405 subjects (221 males, 184 females, mean age 48.9 +/- 12.3 years). The AT was determined during cycle ergometer exercise with continuous respiratory gas measurements. The correlation of heart rate at the AT to resting heart rate, age and gender was analyzed by the multiple regression method. Based on this correlation, a new formula calculating target heart rate was established as 74.8 + 0.76 x (resting heart rate) - 0.27 x (age) + 7.3 x S (male: 0 or female: 1). This formula was then compared to Blackburn's method in 210 subjects (139 males, 71 females, mean age 44.5 +/- 14.4 years). The difference between the new target heart rate and the heart rate at the AT was significantly lower than that between the target heart rate by Blackburn's method [(220 - age) x 0.7] and the heart rate at the AT (8.8 +/- 6.3 vs 12.7 +/- 8.2 beat/min, p < 0.001). The resting heart rate and gender are important factors in determining the target heart rate for exercise. This new formula indicates the adequate exercise training level more accurately in healthy subjects.

Intraperitoneal injection (i.p.) of parathyroid hormone (PTH, 50 micrograms/kg) into young rats (7-day postnatal) induced, within one hour, an increase in the number of osteoclasts which showed well-developed clear zone. Histological observations showed that degranulation of mast cells adjacent to bone surface occurred within 15 min after the injection of PTH. Injection of histamine into rats pretreated with cimetidine, an H2 antagonist of histamine, also induced an increase in the number of active osteoclasts within one hour after the injection of histamine. Furthermore, pretreatment of mice with an H1 antagonist, pyrilamine, completely inhibited the rapid increase in the number of active osteoclasts by PTH. These results suggest that PTH may stimulate osteoclasts to the active form by releasing histamine from mast cells and by stimulating H1 receptors for histamine.