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To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ydbio.2010.03.018 Byline: Akira Satoh (a), Aki Makanae (a), Naoyuki Wada (b) Keywords: Limb regeneration; Limb development; Chick; Amphibian; AER; AEC Abstract: Little effort has been made to apply the insights gained from studies of amphibian limb regeneration to higher vertebrates. During amphibian limb regeneration, a functional epithelium called the apical ectodermal cap (AEC) triggers a regenerative response. As long as the AEC is induced, limb regeneration will take place. Interestingly, similar responses have been observed in chicken embryos. The AEC is an equivalent structure to the apical ectodermal ridge (AER) in higher vertebrates. When a limb bud is amputated it does not regenerate; however, if the AER is grafted onto the amputation surface, damage to the amputated limb bud can be repaired. Thus, the AER/AEC is able to induce regenerative responses in both amphibians and higher vertebrates. It is difficult, however, to induce limb regeneration in higher vertebrates. One reason for this is that re-induction of the AER after amputation in higher vertebrates is challenging. Here, we evaluated whether AER re-induction was possible in higher vertebrates. First, we assessed the sequence of events following limb amputation in chick embryos and compared the features of limb development and regeneration in amphibians and chicks. Based on our findings, we attempted to re-induce the AER. When wnt-2b/fgf-10-expressing cells were inserted concurrently with wounding, successful re-induction of the AER occurred. These results open up new possibilities for limb regeneration in higher vertebrates since AER re-induction, which is considered a key factor in limb regeneration, is now possible. Author Affiliation: (a) Research Core for Interdisciplinary Science (RCIS), Okayama University, 3-1-1 Tsushima-naka, Okayama 700-8530, Japan (b) Department of Molecular and Developmental Biology, Kawasaki Medical School, 577 Matsushima, Kurashiki 701-0192, Japan Article History: Received 26 November 2009; Revised 18 March 2010; Accepted 19 March 2010

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ydbio.2009.11.026 Byline: Shiro Ohgo, Akari Itoh, Makoto Suzuki, Akira Satoh, Hitoshi Yokoyama, Koji Tamura Keywords: Xenopus laevis; Limb regeneration; Proximal-distal axis; hoxa11; hoxa13 Abstract: During limb regeneration, anuran tadpoles and urodele amphibians generate pattern-organizing, multipotent, mesenchymal blastema cells, which give rise to a replica of the lost limb including patterning in three dimensions. To facilitate the regeneration of nonregenerative limbs in other vertebrates, it is important to elucidate the molecular differences between blastema cells that can regenerate the pattern of limbs and those that cannot. In Xenopus froglet (soon after metamorphosis), an amputated limb generates blastema cells that do not produce proper patterning, resulting in a patternless regenerate, a spike, regardless of the amputation level. We found that re-expression of hoxa11 and hoxa13 in the froglet blastema is initiated although the subsequent proximal-distal patterning, including separation of the hoxa11 and hoxa13 expression domains, is disrupted. We also observed an absence of EphA4 gene expression in the froglet blastema and a failure of position-dependent cell sorting, which correlated with the altered hoxa11 and hoxa13 expression. Quantitative analysis of hoxa11 and hoxa13 expression revealed that hoxa13 transcript levels were reduced in the froglet blastema compared with the tadpole blastema. Moreover, the expression of sox9, an important regulator of chondrogenic differentiation, was detected earlier in patternless blastemas than in tadpole blastemas. These results suggest that appropriate spatial, temporal, and quantitative gene expression is necessary for pattern regeneration by blastema cells. Author Affiliation: Department of Developmental Biology and Neurosciences, Graduate School of Life Sciences, Tohoku University, Aobayama Aoba-ku, Sendai 980-8578, Japan Article History: Received 9 July 2009; Revised 19 November 2009; Accepted 20 November 2009

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ydbio.2009.11.023 Byline: Akira Satoh, Gillian M.C. Cummings, Susan V. Bryant, David M. Gardiner Keywords: Axolotl; Limb; Cartilage; Regeneration; Dedifferentiation; Fibroblast; BMP; Neurotrophic factor Abstract: The ability of animals to repair tissue damage is widespread and impressive. Among tissues, the repair and remodeling of bone occurs during growth and in response to injury; however, loss of bone above a threshold amount is not regenerated, resulting in a 'critical-size defect' (CSD). The development of therapies to replace or regenerate a CSD is a major focus of research in regenerative medicine and tissue engineering. Adult urodeles (salamanders) are unique in their ability to regenerate complex tissues perfectly, yet like mammals do not regenerate a CSD. We report on an experimental model for the regeneration of a CSD in the axolotl (the Excisional Regeneration Model) that allows for the identification of signals to induce fibroblast dedifferentiation and skeletal regeneration. This regenerative response is mediated in part by BMP signaling, as is the case in mammals; however, a complete regenerative response requires the induction of a population of undifferentiated, regeneration-competent cells. These cells can be induced by signaling from limb amputation to generate blastema cells that can be grafted to the wound, as well as by signaling from a nerve and a wound epithelium to induce blastema cells from fibroblasts within the wound environment. Author Affiliation: Department of Developmental and Cell Biology, University of California Irvine, Irvine, CA 92697-2305, USA The Developmental Biology Center, University of California Irvine, Irvine, CA 92697-2305, USA Article History: Received 22 August 2009; Revised 24 October 2009; Accepted 16 November 2009

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ydbio.2007.09.021 Byline: Akira Satoh, David M. Gardiner, Susan V. Bryant, Tetsuya Endo Keywords: Axolotl; Limb; Regeneration; Blastema; Fibroblast; Dedifferentiation; Hoxa-13; Msx-2; Prx-1; Tbx-5; Mmp-9 Abstract: Adult urodeles (salamanders) are unique in their ability to regenerate complex organs perfectly. The recently developed Accessory Limb Model (ALM) in the axolotl provides an opportunity to identify and characterize the essential signaling events that control the early steps in limb regeneration. The ALM demonstrates that limb regeneration progresses in a stepwise fashion that is dependent on signals from the wound epidermis, nerves and dermal fibroblasts from opposite sides of the limb. When all the signals are present, a limb is formed de novo. The ALM thus provides an opportunity to identify and characterize the signaling pathways that control blastema morphogenesis and limb regeneration. Our previous study provided data on cell contribution, cell migration and nerve dependency indicating that an ectopic blastema is equivalent to an amputation-induced blastema. In the present study, we have determined that formation of both ectopic blastemas and amputation-induced blastemas is regulated by the same molecular mechanisms, and that both types of blastema cells exhibit the same functions in controlling growth and pattern formation. We have identified and validated five marker genes for the early stages of wound healing, dedifferentiation and blastema formation, and have discovered that the expression of each of these markers is the same for both ectopic and amputation-induced blastemas. In addition, ectopic blastema cells interact coordinately with amputation-induced blastema cells to form a regenerated limb. Therefore, the ALM is appropriate for identifying the signaling pathways regulating the early events of tetrapod limb regeneration. Author Affiliation: Department of Developmental and Cell Biology, Natural Sciences II Division, 4114 Natural Sciences II, University of California Irvine, Irvine, CA 92697-2305, USA Article History: Received 21 May 2007; Revised 29 August 2007; Accepted 13 September 2007

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ydbio.2007.01.019 Byline: Makoto Suzuki, Akira Satoh, Hiroyuki Ide, Koji Tamura Keywords: Xenopus; Limb regeneration; Blastema; Dedifferentiation; Transgenesis; prx1 Abstract: Understanding the mechanisms that control amphibian limb regeneration should allow us to decipher the critical differences between amphibians and humans, which have the limited ability of organ regeneration. However, many issues at the cellular and molecular levels still remain unresolved. We have generated a transgenic Xenopus laevis line that expresses green fluorescent protein (GFP) under the control of mouse prx1 limb enhancer, which directs reporter gene expression in limb mesenchyme in mice, and found that GFP accumulated in blastemal mesenchymal cells of the transgenic froglets after limb amputation. Thus, this transgenic line should provide a new approach to gain insights into the cellular dynamics and signaling pathways involved in limb blastema formation. We have also developed a culture system for forelimb explants of froglets and found that treatment with inhibitors of mitogen-activated protein kinase (MAPK)/extracellular signal-regulated protein kinase (ERK) kinase 1/2 (MEK1/2) and phosphatidylinositol 3-kinase (PI3K) repressed GFP expression. These effects were partially reversible, and down-regulation of GFP was associated with inhibition of cell-cycle progression and induction of ectopic apoptosis. In addition, we found that ERK1/2 and AKT, downstream mediators of MEK1/2 and PI3K pathways, were activated in amputated forelimb stumps. These results demonstrate that MEK/ERK and PI3K/AKT pathways regulate limb blastema formation in the X. laevis froglet. Author Affiliation: Department of Developmental Biology and Neurosciences, Graduate School of Life Sciences, Tohoku University, Aobayama Aoba-ku, Sendai 980-8578, Japan Article History: Received 25 November 2006; Revised 9 January 2007; Accepted 9 January 2007

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ydbio.2005.08.021 Byline: Makoto Suzuki, Akira Satoh, Hiroyuki Ide, Koji Tamura Keywords: Limb regeneration; Xenopus; Nerve dependency; Wound healing; Blastema; Tbx5; Prx1; Msx1; Fgf8; Fgf10 Abstract: Blastema formation, the initial stage of epimorphic limb regeneration in amphibians, is an essential process to produce regenerates. In our study on nerve dependency of blastema formation, we used forelimb of Xenopus laevis froglets as a system and applied some histological and molecular approaches in order to determine early events during blastema formation. We also investigated the lateral wound healing in comparison to blastema formation in limb regeneration. Our study confirmed at the molecular level that there are nerve-dependent and -independent events during blastema formation after limb amputation, Tbx5 and Prx1, reliable markers of initiation of limb regeneration, that start to be expressed independently of nerve supply, although their expressions cannot be maintained without nerve supply. We also found that cell proliferation activity, cell survival and expression of Fgf8, Fgf10 and Msx1 in the blastema were affected by denervation, suggesting that these events specific for blastema outgrowth are controlled by the nerve supply. Wound healing, which is thought to be categorized into tissue regeneration, shares some nerve-independent events with epimorphic limb regeneration, although the healing process results in simple restoration of wounded tissue. Overall, our results demonstrate that dedifferentiated blastemal cells formed at the initial phase of limb regeneration must enter the nerve-dependent epimorphic phase for further processes, including blastema outgrowth, and that failure of entry results in a simple redifferentiation as tissue regeneration. Author Affiliation: Department of Developmental Biology and Neurosciences, Graduate School of Life Sciences, Tohoku University, Aobayama Aoba-ku, Sendai 980-8578, Japan Article History: Received 11 May 2005; Revised 29 July 2005; Accepted 5 August 2005

• Ca2+ leakage through the ryanodine receptor (RyR2) is one of the causes of heart failure. • RyR2-targeting therapy by dantrolene suppresses the Ca2+ leakage through RyR2. • The trial will clarify the efficacy of dantrolene for heart failure and arrhythmia. Leakage of Ca2+ from the sarcoplasmic reticulum (SR) is a critical contributing factor to heart failure pathophysiology. Therefore, reducing SR Ca2+ leaks may provide significant additive benefits when used in combination with conventional therapies. Dantrolene, a drug routinely used to treat malignant hyperthermia, also stabilizes the cardiac isoform of the release channel (RyR2), thus decreasing SR Ca2+ leaks. The purpose of this study is to evaluate the effect of chronic administration of dantrolene on heart failure and lethal arrhythmia in patients with chronic heart failure and reduced ejection fraction in a multicenter, randomized, double-blind, controlled study. Patients with chronic heart failure who had functional status of New York Heart Association class II and III and a left ventricular ejection fraction <40% were treated according to the Japanese Circulation Society, the European Society of Cardiology, and the American Heart Association/the American College of Cardiology guidelines for diagnosis and treatment of acute and chronic heart failure. Patients were randomized and divided into two groups in a double-blind fashion: dantrolene group and placebo group (target sample size: 300 cases). These drugs were administered for 96 weeks. The primary endpoint is cardiovascular death, first hospitalization for exacerbation of heart failure, or lethal arrhythmia [ventricular tachycardia (VT) storm, sustained VT, ventricular fibrillation] for 2 years after starting administration of dantrolene 1 cap (25 mg) three times daily (if not tolerable, two times daily) or matching placebo. This paper presents the rationale and trial design of the study. Recruitment for the study started on 8 December 2017. The results of this trial will clarify the efficacy and safety of dantrolene for ventricular arrhythmia, as well as mortality and morbidity in patients with chronic heart failure and reduced ejection fraction during guideline-directed medical treatment. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Negative magnetorheological effects have been verified experimentally. • The dependence of the negative viscosity on the magnetic field strength has been clarified. • Several situations of the weight percent concentration have been addressed. Abstract In the previous experimental study, we succeeded in verifying that the negative magnetorheological characteristics are observable in a hematite particle suspension, which was predicted by a theoretical study based on the orientational distribution function. The present study further advances the experimental investigation of the negative magnetorheological effect in order to obtain more detailed data of these negative magnetorheological characteristics. The viscosity contribution from magnetic properties has been measured using a cone-plate-type rheometer, located in the uniform area of the magnetic field, under various conditions of the magnetic field strength and the weight percent concentration. It is seen that a contribution to the viscosity of a hematite-glycerol-water dispersion from its magnetic properties, becomes negative and attains to a minimum value, after which the effect decreases and finally becomes positive with increasing magnetic field strength. These characteristics of the negative viscosity are in good agreement with the theoretical prediction that was obtained by the orientational distribution function. [ABSTRACT FROM AUTHOR]

Objective FDG-PET has been shown useful in the staging of malignant lymphoma (ML) and in evaluating treatment outcomes. Serum concentration of soluble interleukin-2 receptor (sIL-2R) has also been shown prognostic in patients with MLs. This study analyzed the clinical possibility of baseline FDG-PET parameters, such as maximum standardized uptake values (SUV max ), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and serum sIL-2R and lactate dehydrogenase (LDH) concentrations, as prognostic variables in patients with oral and neck non-Hodgkin’s lymphoma (NHL). Methods Baseline FDG-PET parameters and serum protein concentrations were correlated with 2-year prognosis in 12 patients with oral and neck NHL. The optimal cutoff values for FDG SUV max, serum sIL-2R and LDH were determined by receiver operating characteristics analyses. Results At 2-year follow up, seven patients remained alive (good prognosis), and five had died (poor prognosis). The median FDG SUV max was significantly higher in the poor than in the good prognosis groups ( P  = 0.04), but serum sIL-2R concentrations did not differ significantly between the two groups ( P  = 0.09). Baseline MTV and TLG were significantly higher in patients with poor than with good prognosis ( P  = 0.02 each). Serum LDH levels was significantly higher in patients with poor than with good prognosis ( P  = 0.01). Univariate logistic regression analysis showed significant correlations between FDG SUV max and patient prognosis ( P  = 0.04, odds ratio, 23.4). Conclusion Comprehensive evaluation of baseline FDG SUV max may have possibility for predicting the prognosis of patients with oral and neck NHLs. [ABSTRACT FROM AUTHOR]

Purpose: This study evaluated short-term and long-term changes in bone height after mandibular reconstruction using an osteotomized fibula graft, with the aim of identifying factors associated with atrophy of the graft in an elderly population.Patients and Methods: This retrospective study involved patients who underwent mandibular reconstruction using a free vascularized fibula graft from 2005 through 2015 and had at least 12 months of follow-up. Postoperative panoramic radiographs were used to measure bone height at standardized locations on each segment of the graft at 1 year postoperatively and at later follow-up.Results: The sample was composed of 30 patients (15 men, 15 women; mean age, 62.6 years; age range, 50 to 80 years). According to the HCL classification (H, hemimandibular segment including the condyle; C, central segment including both mandibular canine teeth; L, lateral segment without the condyle), mandibular defect types were L (n = 19), LC (n = 7), LCL (n = 3), and H (n = 1). There were 0 to 3 segmental osteotomies with the fibula graft. None of the patients received an osseointegrated dental implant during a mean follow-up of 4.0 years (range, 1.5 to 9.7 yr). All patients underwent reconstruction of the mandibular body, 10 of whom also underwent reconstruction of the mandibular ramus. Atrophy of the fibula graft was observed in 9.9 and 15.0% of the body segment and 5.9 and 6.6% of the ramal segment at 1 year postoperatively and at later follow-up, respectively. Graft hypertrophy occurred in the ramal segment in 2 patients. Multivariate analysis showed a significantly higher rate of graft atrophy in women than in men at later follow-up (P = .033).Conclusions: Fibula grafts showed long-term stability, and in 2 cases even a gain in bone height, in this elderly population. Female gender was identified as a risk factor for atrophy of the fibula bone graft in the body segment of the reconstructed mandible. [ABSTRACT FROM AUTHOR]

In the present study, we address a suspension composed ferromagnetic rod-like particles to elucidate a regime change in the aggregate structures and the magneto-rheological characteristics. Monte Carlo simulations have been employed for investigating the aggregate structures in thermodynamic equilibrium, and Brownian dynamics simulations for magneto-rheological features in a simple shear flow. The main results obtained here are summarized as follows. For the case of thermodynamic equilibrium, the rod-like particles aggregate to form thick chain-like clusters and the neighboring clusters incline in opposite directions. If the external magnetic field is increased, the thick chain-like clusters in the magnetic field direction grow thicker by adsorbing the neighboring clusters that incline in the opposite direction. Hence, a significant phase change in the particle aggregates is not induced by an increase in the magnetic field strength. For the case of a simple shear flow, even a weak shear flow induces a significant regime change from the thick chain-like clusters of thermodynamic equilibrium into wall-like aggregates composed of short raft-like clusters. A strong external magnetic field drastically changes these aggregates into wall-like aggregates composed of thick chain-like clusters rather than the short raft-like clusters. The internal structure of these aggregates is not strongly influenced by a shear flow, and the formation of the short raft-like clusters is maintained inside the aggregates. The main contribution to the net viscosity is the viscosity component due to magnetic particle-particle interaction forces in relation to the present volumetric fraction. Hence, a larger magnetic interaction strength and also a stronger external magnetic field give rise to a larger magneto-rheological effect. However, the dependence of the viscosity on these factors is governed in a complex manner by whether or not the wall-like aggregates are composed mainly of short raft-like clusters. An increase in the shear rate functions to simply decrease the effect of the magnetic particle-particle and the particle-field interactions. [ABSTRACT FROM AUTHOR]

Background Dabigatran etexilate (DE), an effective direct oral anticoagulant for patients with atrial fibrillation (AF), should be carefully used in patients with renal insufficiency. Data on the safety of DE in Japanese “real world” patients with mildly impaired renal function are limited. We hypothesized that low-dose DE (110 mg, twice daily) could be safely used in Japanese AF patients with mildly impaired renal function compared to those with preserved renal function. Methods and results One hundred ninety-six consecutive AF patients taking low-dose DE were retrospectively enrolled in this study, and were divided into two groups: preserved creatinine clearance (CCr ≥50 ml/min; n = 127) and reduced CCr (30–49 ml/min; n = 69). Baseline characteristics including CHADS 2 , CHA 2 DS 2 -VASc, and HAS-BLED scores were evaluated. Activated partial thromboplastin time (aPTT) was measured as a surrogate marker of the anticoagulant activity of DE, which was evaluated at 661 time points in total and the data were divided into five time windows after the last DE intake. The incidence of bleeding complications was compared between the two groups of reduced and preserved CCr. Reduced CCr group showed higher age (76.9 ± 6.3 years vs. 67.6 ± 6.7 years), higher CHADS 2 (2.6 ± 1.4 vs. 1.8 ± 1.2), higher CHA 2 DS 2 -VASc (4.3 ± 1.6 vs. 3.2 ± 1.6), and higher HAS-BLED (2.3 ± 1.0 vs. 2.0 ± 1.0) scores in comparison with preserved CCr group ( p < 0.01, respectively). There was no difference in aPTT over the entire time windows between the two groups. The incidence of total bleeding events was not significantly different between the two groups (reduced vs. preserved CCr = 2/69 vs. 2/127). Conclusion Low-dose DE was safe in AF patients with mildly reduced CCr. [ABSTRACT FROM AUTHOR]

It is known that the efficacy of catheter ablation for atrial fibrillation (AF) is high, but cardiac tamponade may occur in 1–2% cases. Even in such cases, fatal condition can be avoided by appropriate drainage, but reversal of anticoagulation therapy might also be necessary. Here, we report a case of use of idarucizumab for cardiac tamponade during AF ablation. Although the drainage with pericardial centesis should be selected, we could not perform because echo free space was too thin at least at the precordial or apical side of the ventricle. Fortunately, dabigatran reversal by idarucizumab suppressed cardiac tamponade progress and the patient recovered without undergoing any invasive procedures. The pericardial drainage must be the principal therapy for cardiac tamponade, but reversal of anticoagulant might be helpful for patients' recovery. It might be thought that dabigatran, the only direct oral anticoagulant with a specific reversal agent, should be the safest choice in case of risk for bleeding complications such as AF ablation. < Learning objective: Cardiac tamponade is one of the complications of catheter ablation for atrial fibrillation (AF). In such cases, fatal condition can be avoided by appropriate drainage, but reversal of anticoagulation therapy might be necessary. Drainage with pericardial centesis was not selected because echo free space was too thin. Dabigatran reversal by idarucizumab suppressed cardiac tamponade progress. It was thought that dabigatran would be the safest choice in case of bleeding complications during AF ablation.> [ABSTRACT FROM AUTHOR]

Purpose: Recent reports have documented the appearance of Brugada-type ST elevation in cases of overdose of antiepileptic drugs (AEDs). However, little is known about changes on electrocardiographs (ECGs) during AED use at therapeutic doses. AEDs may cause Brugada-type ST elevation or J-wave-like intraventricular conduction delays through an ion channel-blocking effect. In the present study, we sought to elucidate ECG abnormalities in patients on AED therapy.Methods: The study population consisted of 120 consecutive patients with epilepsy who continued to take AEDs and had ECGs recorded during these therapies. Their clinical background and ECGs were retrospectively analyzed. Brugada-type ST elevation was classified according to the consensus report on Brugada syndrome. A J-wave-like ECG abnormality was defined as the appearance of notching or slurring of the QRS complex (>0.1mV) in the inferior/lateral leads.Results: Of the 120 patients, 15 (12.5%) exhibited Brugada-type ST elevation and 35 (29.2%) showed a J-wave-like ECG abnormality. Polytherapy with sodium channel-blocking AEDs (e.g., carbamazepine, phenytoin, lamotrigine) was more frequently observed in patients with Brugada-type ST elevation (p=0.048). However, the serum concentrations of these medicines did not differ between patients with and without ECG abnormalities (carbamazepine: 7.9±4.1 vs. 7.2±5.9μg/dL; phenytoin: 12.7±4.1 vs. 15.5±9.5μg/dL, NS).Conclusion: ST-T abnormalities were frequently seen in patients using AEDs. The presence of Brugada-type ST elevation was associated with polytherapy with sodium channel-blocking AEDs. [ABSTRACT FROM AUTHOR]

Severe fever with thrombocytopenia syndrome (SFTS) caused by the SFTS virus (SFTSV), a novel phlebovirus belonging to the family Bunyaviridae, was reported in China for the first time in 2009. We observed two cases where the SFTSV was isolated for the first time in Nagasaki, Japan, in 2005. Two males in their 60s, a farmer and a hunter, respectively, living in Nagasaki developed SFTS during the same period. The patients developed similar clinical symptoms and signs, such as fever, loss of consciousness, and multiple organ dysfunction. The farmer died and the hunter survived. A retrospective diagnosis of SFTS was made in 2013, and genetic analysis revealed that the patients were infected with different SFTSV strains. Retrospective analysis of cytokine production in non-fatal case revealed interleukin (IL)-6, IL-8 and interferon-γ level of acute phase was low and could be potential prognostic factors. As there are no epidemiological studies of positive rate of SFTSV antibody in people living in endemic areas in Japan, a field study was performed. Volunteers at high risk for tick bites, such as hunters, farmers, and soldiers, were recruited in 6 regions, including the areas where the SFTS cases occurred. Three hundred and twenty six volunteers in Nagasaki prefecture were examined and none of these tested positive for the SFTSV antibody. Our data indicates that the risk for SFTSV infection is not high in Nagasaki prefecture. Further collection of blood samples from endemic areas is warranted for the prevention of SFTSV infection. [ABSTRACT FROM AUTHOR]

Radiotherapy for oral cancer that has caused jaw absorption has been reported occasionally to result in bone regeneration, but this regeneration is generally partial. We report a case of marked bone production from the mandibular head to the reconstructed fibula after chemoradiotherapy for the recurrent tumor. A 50-year-old man had undergone upper neck dissection, mandibular segmental resection and reconstruction using a free vascularized fibula osteocutaneous flap for a primary intraosseous squamous cell carcinoma in the right mandible. Six months later, CT showed tumor recurrence with bone destruction from the mandibular head to the reconstructed fibula. He received chemoradiotherapy, consisting of radiotherapy (70 Gy in 28 fractions) with docetaxel (10 mg/m 2 once weekly for 6 weeks) and cisplatin (4 mg/m 2 daily for 28 days). Marked bone regeneration was observed, with the mandibular head and fibula almost completely recovering from bone destruction. At present, 7 years later, there has been no sign of tumor recurrence. [ABSTRACT FROM AUTHOR]

Object A modified World Federation of Neurosurgical Societies scale (m-WFNS scale) for aneurysmal subarachnoid hemorrhage (SAH) recently has been proposed, in which patients with Glasgow Coma Scale (GCS) scores of 14 are assigned to grade II and those with GCS scores of 13 are assigned to grade III regardless of the presence of neurologic deficits. The study objective was to evaluate outcome predictability of the m-WFNS scale in a large cohort. Methods This was a multicenter prospective observational study conducted in Japan. A total of 1656 patients with SAH were registered during the 2.5-year study period, and the outcome predictability, using the Glasgow Outcome Scale (GOS) and modified Rankin Scale (mRS) scores at discharge and at 90 days after onset, was evaluated by comparing the m-WFNS with the original WFNS scale. We focused on whether significant differences in these scores were present between the neighboring grades. Results In the m-WFNS scale, significant difference between any neighboring grades was observed both in the mean GOS and mRS scores at 90 days except between grades III/IV. However, differences were not significant between grades II/III and between grades III/IV in the original WFNS scale. Conclusions SAH-induced brain injury may be substantially severer in patients with GCS 13 than those with GCS 14, which may explain why grade III patients faired significantly worse than grade II patients by the modified WFNS scale. Although further validation is necessary, the m-WFNS scale has a potential of providing neurosurgeons with simpler and more reliable prognostication of patients with SAH. [ABSTRACT FROM AUTHOR]

We have theoretically investigated the particle orientational and rheological properties of a dilute suspension composed of spindle-like hematite particles under a simple shear flow. In the present study, we have derived the basic equation of the orientational distribution function by taking into account the spin Brownian motion about the particle axis. The basic equation has been solved numerically in order to investigate the influence of the shear rate, the magnetic field strength, and the rotational Brownian motion on the orientational distribution and rheological properties. For a very strong magnetic field applied in the shear flow direction, the rotational motion of the particle is restricted in a plane normal to the shearing plane due to the spin rotational Brownian motion. Although the negative viscosity was observed in the previous study, in the present case the orientational properties of the particle give rise to positive viscosity. The viscosity becomes large with increasing magnetic field strength. The viscosity due to magnetic properties does not occur in the situation of a magnetic field applied in the direction of the angular velocity vector of a simple shear flow. [ABSTRACT FROM AUTHOR]

Highlights: [•] The mass cultivation process of Fistulifera sp. JPCC DA0580 was developed. [•] A commercial (48,000L) indoor culture factory was applied for production prediction. [•] The algae mass productivity was calculated as 68.7tha−1 year−1. [•] Annual algal oil productivity was estimated to be 33.3tha−1 year−1. [ABSTRACT FROM AUTHOR]

Abstract: This article discusses a case of bilateral multiple cervical lymph node metastases of oncocytic carcinoma—an extremely rare neoplasm of the salivary glands—that was found in a 71-year-old Japanese female patient who presented with a painless swelling in the bilateral submandibular regions. Computed tomography demonstrated enlarged bilateral multiple lymph nodes. Multiple metastases to bilateral cervical lymph nodes were clinically suspected, and bilateral neck dissections were performed. The tumor tissue adjoined the submandibular gland with a thin fibrous connective tissue capsule. Histologically, the tumor was predominantly composed of large, round to polyhedral cells with fine granular eosinophilic cytoplasm, which were arranged in solid sheets, islands and cords. Ultrastructural analysis revealed numerous mitochondria with abnormal shapes packed in the cytoplasm of the neoplastic cells. The tumor was diagnosed as oncocytic carcinoma of the submandibular gland with bilateral multiple cervical lymph node metastases. The tumor developed neither recurrence nor distant metastasis for eight years after the operation. [Copyright &y& Elsevier]

Abstract: Although tetanus is a rare condition in Japan, it still has a high mortality rate. As patients show trismus, dysphagia, and rigidity of the neck, they tend to consult specialists in dentistry, otolaryngology, and orthopedics. Sometimes, accurate diagnosis of tetanus is not made at the first consultation. Here, we report a case of tetanus referred to our department that was appropriately managed with early diagnosis. Moreover, we reviewed the literature concerning 47 patients with tetanus from 2000 in Japan regarding which department they visited first, the initial diagnosis, and clinical courses of the patients. The orders of the first visiting departments were otolaryngology, internal medicine, general surgery, orthopedics, emergency, and dentistry. Only 6 patients (6/47: 13%) were correctly diagnosed as having tetanus at the first diagnosis. In contrast, the remaining 41 cases did not receive a correct diagnosis at the first visit. Twenty patients (20/47: 43%) were diagnosed as “unknown etiology”. After additional consultations, the final diagnosis of tetanus was made mainly in dentistry, emergency, otolaryngology, and internal medicine. As for the treatment, the patients received actual treatment for tetanus mainly in the department of emergency, internal medicine, anesthesiology, and neurological medicine. Thirty-two of the patients (32/47: 68%) entered the ICU. In conclusion, head and neck specialists should be equipped to make correct diagnosis in patients with tetanus. Close communication with specialists in the ICU is important, along with education of doctors, staff, and students regarding the importance of rapid diagnosis of tetanus. [Copyright &y& Elsevier]

Background: Although we have previously reported that the presence of paroxysmal atrial fibrillation (AF) is an independent risk factor for rehospitalization in patients with congestive heart failure (CHF) in a population from 1996 to 2002, the impact of AF configuration as a risk factor in a more recent population remains to be clarified. Methods and results: 319 patients with CHF admitted to our institute in 2006-2007 were retrospectively evaluated. The patients were divided into 3 groups in accordance with their basic cardiac rhythm, i.e. sinus rhythm (n = 210), chronic AF (n = 68), and paroxysmal AF (n =41 ). During the follow-up period of 19 ± 17 months, there was no significant difference in mortality or rehospitalization events among the 3 groups (p = 0.542). In the multivariate analysis, no administration of β-blockers was the only independent risk factor for rehospitalization due to CHF exacerbation. Conclusions: The clinical impact of AF configuration as a risk factor of rehospitalization due to CHF exacerbation was considered to be decreased in recent years. [ABSTRACT FROM AUTHOR]

Objective: We have previously reported that the histologic mode of invasion of oral squamous cell carcinoma (OSCC) is a significant risk factor for pain. Here we sought to determine whether pain is a risk factor for poor prognosis in patients with OSCC. Study design: We evaluated the relationships between overall survival rates and clinicopathologic variables, including gender, age, T- and N-stages, pathologic findings, and pain in 109 consecutive patients with untreated OSCC. Results: Of these 109 patients, 40 (37%) reported spontaneous pain. Univariate analysis showed that the overall survival rates of patients with spontaneous pain was significantly lower than those of patients without pain (P = .002). Multivariate analysis revealed that spontaneous pain and N-stage were significant independent predictors of overall survival rates. Conclusions: This is the first report showing that spontaneous pain before treatment may be associated with poor prognosis in patients with OSCC. [Copyright &y& Elsevier]

Objective: The aim of this study was to elucidate changes in interleukin-6 (IL-6) levels in whole saliva during the treatment of patients with oral squamous cell carcinoma (OSCC). Study design: Twenty-nine consecutive inpatients with OSCC were enrolled. Stimulated saliva was collected just after hospitalization (period 1), just before main treatment (surgery in 26 cases; period 2), and at the time of discharge (period 3). The mean intervals were 11 ± 8 days between periods 1 and 2 and 30 ± 18 days between periods 2 and 3. Nineteen age-matched healthy control subjects were also recruited. Interleukin-6 concentrations were measured by a highly sensitive chemiluminescent enzyme immunoassay. Results: Interleukin-6 was detected in 23 out of 29 samples in the OSCC group in period 1. The concentration of IL-6 was significantly higher in the OSCC group (mean 20.1 ± 36.3 pg/mL) than in the control subjects (0.6 ± 0.8 pg/mL; P = .003). The mean concentration of IL-6 at period 2 was 43.6 ± 95.6 pg/mL, significantly higher than at period 1 (P = .002), and at period 3 was 17.1 ± 27.6 pg/mL (P = .52 [compared with period 2]). Conclusions: Interleukin-6 was up-regulated in saliva in the OSCC patients. The IL-6 level tended to increase before treatment, and it returned to baseline levels after treatment. [ABSTRACT FROM AUTHOR]

Neuromuscular electrical stimulation (NMES) is one of the few exercise modes that have been confirmed to be effective for advanced heart failure patients. Previous clinical trials that verified the effects of NMES excluded patients with implantable cardioverter defibrillators (ICDs). We investigated whether NMES to leg muscles could be applied in heart failure patients implanted with ICDs. As a result, we found that NMES could be conducted without any instances of electromagnetic interference. NMES to leg muscles could be applied safely to ICD patients if the aforementioned common stimulation methods were used with sufficient monitoring during NMES. [ABSTRACT FROM AUTHOR]

Abstract: The sensitivity of nine marine microalgal species (consisting of five divisions and seven genera) to the five heavy metals, Cu(II), As(V), Sb(III), Pb(II) and Cd(II) was studied by using a fluorometric growth-inhibition assay with 96-well microplates. The algal strains studied were Cylindrotheca sp. and the LPP group that respectively characterize aggregating and filamentous types, and Chlorococcum littorale, Chlorococcum sp., Isochrysis galbana, Tetraselmis tetrathele, Heterocapsa sp., Synechococcus sp. and Prasinococcus sp. for types that occur as single cells. A good linear relationship was observed between the chlorophyll a concentration and intensity of chlorophyll fluorescence (485-nm excitation filter and 645-nm emission filter) when the chlorophyll a concentration was within the range of 0.10–5.0 μg ml−1. A starting cell concentration of 0.10 or 0.25 μg Chl a ml−1 was therefore selected. In accordance with OECD 201 standard procedures, the IC50 value (concentration of a metal producing 50% growth inhibition relative to the control) was determined 72 h after adding a heavy metal by using the biomass integral. The microplate toxicity test used in this study is considered to be applicable to diverse algae, not only enumerating species but also hardly enumerating ones. [Copyright &y& Elsevier]

Objective: Sequential postoperative salivary interleukin-6 (IL-6) concentrations were examined in patients with oral squamous cell carcinoma (OSCC) who had early or late locoregional recurrences or those who did not.Study Design: Twenty-seven consecutive patients with OSCC were originally included in the study. All patients underwent radical surgery. Four saliva samples were collected before (periods I and II) and after (periods III and IV) surgery, and IL-6 concentrations were measured.Results: Although postoperative (period III: at the time of discharge) salivary IL-6 level was significantly higher in patients with early locoregional recurrence (P = .02) than in those without, no such relationships were observed for preoperative IL-6 concentrations (periods I and II). Postoperative (period IV: 24 months after surgery) IL-6 level was significantly higher in patients with late locoregional recurrence (P = .03) than in those without, but no such relationships were observed for IL-6 concentrations in periods I, II, and III.Conclusions: Sequential postoperative salivary IL-6 concentration may be a useful marker for diagnosis of early and late locoregional recurrence in OSCC. [ABSTRACT FROM AUTHOR]