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Com o crescimento na quantidade de micro e pequenas empresas e de profissionais autônomos no país, evidencia-se a necessidade da criação de estratégias para aumentar a competitividade otimizando a produtividade e as vendas de produtos no varejo. A Pesquisa Operacional (PO), através de técnicas como a de Programação Linear (PL), busca auxiliar na tomada de decisão e planejamento estratégico no planejamento da produção. A PO foi desenvolvida inicialmente com objetivos militares e os conceitos estão atualmente presentes em diversas áreas estratégicas de grandes empresas, e podem ser adaptadas para os micro-empreendedores. Neste contexto, este estudo objetivou estudar a maximização dos lucros de um produtor de trufas de chocolate na cidade de Suzano, no qual se utilizou os recursos de PO e PL para traçar as quantidades ideais de trufas para cada sabor deveria ser produzida a fim de que os lucros aumentassem. Para isso, montou-se o modelo matemático e com o auxílio do Solver, conseguiu-se a resposta para a problemática em questão.

Certain catecholamine metabolites exert significant pharmacological effects. Herein, we evaluated the pharmacological activities of catecholamine metabolites in the rat thoracic aorta, prostate, and spleen to determine whether these metabolites affect the contractile functions of smooth muscle tissue via direct action on α-adrenoceptors and α-adrenoceptor subtypes. Among the catecholamine metabolites examined, normetadrenaline and metadrenaline (10−4 M each) produced relatively strong contractions in the rat thoracic aorta. Maximum aortic contractions induced by normetadrenaline (≈70% of phenylephrine (3 × 10−7 M)-induced contractions) and metadrenaline (≈45%) were significantly smaller than those induced by phenylephrine (≈95%). Normetadrenaline and metadrenaline (10−4 M each) inhibited phenylephrine (3 × 10−7 M)-induced aortic contractions, which were not affected by propranolol (10−6 M), by 5–20%. Normetadrenaline- and metadrenaline (3 × 10−5 M each)-induced aortic contractions were strongly inhibited by prazosin (10−8 M; an α1-adrenoceptor antagonist) and BMY 7378 (10−8–10−7 M; a selective α1D-adrenoceptor antagonist). Metadrenaline (3 × 10−5 M)-induced aortic contractions were also significantly inhibited by silodosin (10−9 M; a selective α1A-adrenoceptor antagonist). Normetadrenaline and metadrenaline (3 × 10−5 M each) caused silodosin (10−9 M)-sensitive prostate contractions but did not cause a prominent spleen contraction. Maximum prostate contractions induced by metadrenaline (≈100% of phenylephrine (3 × 10−5 M)-induced contractions) were nearly identical to those induced by phenylephrine (≈100%) but were significantly larger than those induced by normetadrenaline (≈80%). These findings suggest that normetadrenaline and metadrenaline act as a partial α1D/α1A-adrenoceptor agonist and partial α1D-adrenoceptor/full α1A-adrenoceptor agonist, respectively, functioning as adrenaline system stabilizers in α1D/α1A-adrenoceptor-abundant smooth muscle tissues.

Object We aimed to identify the β-adrenoceptor (β-AR) subtypes involved in isoprenaline-induced relaxation of guinea pig colonic longitudinal smooth muscle using pharmacological and biochemical approaches. Methods Longitudinal smooth muscle was prepared from the male guinea pig ascending colon and contracted with histamine prior to comparing the relaxant responses to three catecholamines (isoprenaline, adrenaline, and noradrenaline). The inhibitory effects of subtype-selective β-AR antagonists on isoprenaline-induced relaxation were then investigated. Results The relaxant potencies of the catecholamines were ranked as: isoprenaline > noradrenaline ≈ adrenaline, whereas the rank order was isoprenaline > noradrenaline > adrenaline in the presence of propranolol (a non-selective β-AR antagonist; 3 × 10-7 M). Atenolol (a selective β1-AR antagonist; 3 × 10-7-10-6 M) acted as a competitive antagonist of isoprenaline-induced relaxation, and the pA2 value was calculated to be 6.49 (95% confidence interval: 6.34-6.83). The relaxation to isoprenaline was not affected by ICI-118,551 (a selective β2-AR antagonist) at 10-9-10-8 M, but was competitively antagonized by 10-7-3 × 10-7 M, with a pA2 value of 7.41 (95% confidence interval: 7.18-8.02). In the presence of propranolol (3 × 10-7 M), the relaxant effect of isoprenaline was competitively antagonized by bupranolol (a non-selective β-AR antagonist), with a pA2 value of 5.90 (95% confidence interval: 5.73-6.35). Conclusion These findings indicated that the β-AR subtypes involved in isoprenaline-induced relaxation of colonic longitudinal guinea pig muscles are β1-AR and β3-AR.

Semi-cones of rings determine the partial orders in the rings. We consider semi-cones in the direct product rings and the product extension rings, inducing finitely generated semi-cones. In particular, we give characterizations for semi-cones of the direct product rings and the basic product extension rings of the ring of integers.

To elucidate the mechanism whereby distigmine, an underactive bladder remedy, potentiates urinary bladder contractions long-lastingly, the inhibition of recombinant human acetylcholinesterase (rhAChE) by distigmine was investigated. A centrifugal ultrafiltration device, Nanosep® 10K, was used to separate rhAChE and a bound inhibitor from an unbound inhibitor, reaction substrate, and reaction product. This allowed the same aliquot of rhAChE to be repeatedly assayed for up to 48 h to confirm the long-lasting binding of an inhibitor. Cholinesterase (ChE) inhibitors, distigmine, pyridostigmine, neostigmine, and ambenonium, were tested. The dissociation rate constant (kdiss) and dissociation half-life (t1/2) of each inhibitor were determined based on the changes in rhAChE activity. Within 2-4 h after removing pyridostigmine, neostigmine, or ambenonium, the rhAChE activity was restored to the control levels. The kdiss values for pyridostigmine, neostigmine, and ambenonium were calculated to be 0.51±0.05, 0.66±0.03, and 1.41±0.08 h-1, and the t1/2 values were calculated to be 1.36, 1.05, and 0.49 h, respectively. With distigmine, the rhAChE activity initially dropped to 17% of that in the control and then slowly recovered to only 50% by 48 h after drug removal. The kdiss and t1/2 values of distigmine were calculated to be 0.012±0.001 h-1 and 57.8 h, respectively. Based on the t1/2 values, distigmine was judged to dissociate from acetylcholinesterase (AChE) 40-120-fold slower than the other ChE inhibitors did. This may explain the long-lasting potentiation of urinary bladder contractions and motility by distigmine as a treatment for an underactive bladder.

Scars developing on body surfaces not only restrict body movement, but are also problematic from a cosmetic standpoint. Hence, revision is conducted by removing the scar and re-suturing the resultant defects. In performing scar revision, care should be taken to prevent the re-sutured wounds from developing hypertrophy again. Scars often present a pattern where hard, red parts are separated by soft parts in between. As the hard and soft parts may be analogized as islands and seas respectively, we call this the “Island-Like” scar. Two strategies can be taken to treat scars of this type. The first is to remove the entire scar—including both hard and soft parts; the second is to remove only the hard parts and leave the soft parts untouched. The authors conducted a biomechanical study using finite element analyses and found that as a body moves, greater stresses occur in the peri-wound regions with the first strategy than with the second strategy. A wound’s likelihood to develop hypertrophy increases as the stresses working on it increase. Hence, it is hypothesized that the second strategy carries less risk of the operated wounds developing re-hypertrophy than the first strategy. Based on this logic, in performing scar revision for scars consisting of hard and soft parts, it is recommended only to remove only hard parts and not to operate on soft parts in between.

Highlights • Different strategies are available for the re-correction after pectus excavatum surgery. • We cultured and propagated chondrocytes taken from a patient’s auricular cartilage. • The cultured chondrocytes are transplanted to the concave part of the chest. • The chest shape improved and the transplanted cells consolidated, forming part of the chest wall. • Transplantation of cultured chondrocytes is a useful treatment for pectus excavatum., Introduction For some cases of pectus excavatum, ideal chest shape cannot be achieved solely by performing the Nuss procedure. This manuscript presents a case where the residual deformity following Nuss was corrected using injection-transplantation of cultured autologous chondrocytes. Presentation of case The treatment was performed for an 18-year-old male, who sought improvement of his chest shape after previously undergoing the Nuss procedure. A 1 cm2 auricular cartilage piece was harvested from his ear. Chondrocytes were isolated from the cartilage piece and were cultured. The cultured chondrocytes were processed into gel form and were injection-transplanted to the deformed region of the patient's chest. The grafted chondrocytes consolidated in one month, presenting elasticity equivalent to ordinary costal cartilage. The patient's chest remains in an optimal shape after a one-year postoperative follow up. Discussion Secondary correction of the chest deformity after previous operation for pectus excavatum is often tricky, because of the possible adhesion of the lungs or pericardium with the thoracic wall. Transplantation of cultured autologous chondrocytes does not require intra-thoracic maneuvers, and so is less invasive than other surgical interventions. Hence, priority can be placed, in some cases, on the chondrocyte transplantation rather than the re-correction of the thorax with the Nuss procedure or Ravitch procedure. Conclusion Transplantation of cultured autologous chondrocytes is recommended as a useful option for secondary correction of chest deformity after the Nuss procedure.

Aim To determine the effectiveness of ventilations in bystander cardiopulmonary resuscitation (BCPR) and to identify the factors associated with ventilation-only BCPR. Methods From out-of-hospital cardiac arrest (OHCA) data prospectively collected from 2005 to 2011 in Japan, we extracted data for 210,134 bystander-witnessed OHCAs with complete datasets but no prehospital involvement of physician [no BCPR, 115,733; ventilation-only, 2093; compression-only, 61,075; and conventional (compressions+ventilations) BCPR, 31,233] and determined the factors associated with 1-month neurologically favourable survival using simple and multivariable logistic regression analyses. In 91,885 patients with known BCPR durations, we determined the factors associated with ventilation-only BCPR. Results The rate of survival in the no BCPR, ventilation-only, compression-only and conventional group was 2.8%, 3.9%, 4.5% and 5.0%, respectively. After adjustment for other factors associated with outcomes, the survival rate in the ventilation-only group was higher than that in the no BCPR group (adjusted OR; 95% CI, 1.29; 1.01–1.63), but lower than that in the compression-only (0.76; 0.59–0.96) or conventional groups (0.70; 0.55–0.89). Conventional CPR had the highest OR for survival in almost all OHCA subgroups. The adjusted OR (95% CI) for survival after dividing BCPR into ventilation and compression components was 1.19 (1.11–1.27) and 1.60 (1.51–1.69), respectively. Older guidelines, female sex, younger patient age, bystander-initiated CPR without instruction, early BCPR and short BCPR duration were associated with ventilation-only BCPR. Conclusions Ventilation is a significant component of BCPR, but alone is less effective than compression in improving neurologically favourable survival after OHCAs.

Distigmine bromide (distigmine), a reversible, long-lasting cholinesterase (ChE) inhibitor, is used for the treatment of underactive bladder in Japan and has been shown to potentiate urinary bladder (UB) contractility. We studied the duration of distigmine's potentiating effects on acetylcholine (ACh)-induced UB contraction and its inhibitory effects on ChE activity, and compared that with those of other ChE inhibitors (neostigmine, pyridostigmine, and ambenonium). The duration of potentiating/inhibitory effects of ChE inhibitors, including distigmine, on ACh-induced guinea pig UB contraction/ChE activity was evaluated for 12 h following washout. Dissociation rate constants (k) of the inhibitors were also tentatively calculated based on the time courses of their ChE inhibitory effects. The potentiating effect of distigmine (10-6 M) on ACh-induced UB contraction and its inhibitory effect on ChE activity were significantly sustained 12 h after washout. The potentiating effect of other ChE inhibitors on ACh-induced UB contraction, however, was sustained only until 3 h after washout. The ChE inhibitory effects of these inhibitors dissipated in a time-dependent manner after washout, with more than 75% of ChE activity restored by 4 h after washout. The k values of ChE inhibitors approached 0.50 h-1, except for distigmine, where k could not be determined. Compared with that of other ChE inhibitors, the potentiating effect of distigmine on UB contractile function was significantly more sustainable following washout, which was likely associated with its corresponding long-lasting ChE inhibitory effect. Distigmine may associate more strongly with UB ChE than other ChE inhibitors, which would partly explain its sustained effects.

Distigmine is a cholinesterase (ChE) inhibitor used for the treatment of detrusor underactivity in Japan. Distigmine's pharmacological effects are known to be long-lasting, but the duration of its effect on urinary bladder contractile function has not been fully elucidated. The present study aimed to determine these effects in relation to the plasma concentrations of distigmine and its inhibition of ChE activities in blood, plasma, and bladder tissue. Intravesical pressures were recorded in anesthetized guinea-pigs for 12 h after the intravenous administration of saline or distigmine (0.01-0.1 mg/kg). Plasma distigmine concentrations were measured by liquid chromatograph-tandem mass spectrometry (LC-MS/MS), while ChE activities were assayed using 5,5'-dithiobis(2-nitrobenzoic acid). Distigmine (0.1 mg/kg) significantly increased the maximum intravesical pressure at micturition reflex for 12 h post-administration. In contrast, plasma distigmine was only detectable for 6 h post-administration in these animals and a one-compartment model calculated an elimination half-life of 0.7 h. However, bladder and blood acetylcholinesterase activities were significantly inhibited for 12 h after distigmine administration, although plasma ChE activities were not affected. The pharmacodynamic effects of distigmine thus persisted after its elimination from the circulation, indicating that it may bind to bladder acetylcholinesterase, producing sustained enzyme inhibition and enhancement of bladder contractility.

Background Neutropenia has been reported with interleukin-6 (IL-6) pathway inhibitors and could potentially be associated with increased rates of infection. The reduced neutrophil counts seen with IL-6 inhibitors may be due to effects on margination of circulating neutrophils as opposed to a decrease in bone marrow production or reduced survival. Efficacy of sirukumab (SIR), a human anti-IL-6 cytokine monoclonal antibody, has recently been shown in several phase 3 trials. Objectives To assess incidence of neutropenia from completed and ongoing SIRROUND clinical studies. Methods Neutrophil counts were compared for SIR 50mg q4w and 100mg q2w doses vs placebo (pbo) in the pbo-controlled period (Wks 0–18) of 2 phase 3 trials and in long-term analysis for the 5-trial, phase 3 program. Results 2926 pts received SIR for up to 3.4y with a median duration of 1.46y. For the 18-wk pbo-controlled period, neutropenia was more frequent in both SIR groups compared with pbo. Across all groups, the majority of the decreases in neutrophil counts were National Cancer Institute Common Terminology Criteria for Adverse Events grade 0/1, within the normal range, and the incidence of grade 3/4 decreases was low across groups (Table). Neutropenia began at Wk 2 and persisted through the study period. In long-term analysis, the proportions of pts with grade 1, 2, or 3 neutropenia were slightly higher than in the 18-wk pbo-controlled period, suggesting the majority of events occurred early. No dose relationship was observed in the grade or frequency of neutropenia. Grade 3/4 neutropenia was mostly transient and resolved after interrupting the dose or resolved within the dosing interval such that no change in dose schedule was required. The majority of grade 4 decreases in neutrophils were not correlated with infections; 2 cases of serious infections occurred with grade 4 neutropenia. The distribution of neutropenia by grade was similar in pts who did or did not use disease-modifying antirheumatic drugs (DMARDs) at baseline. Conclusions Across phase 3 studies, there was no dose effect of SIR on neutropenia, and the use of DMARDs did not have an apparent effect on neutropenia. The majority of grade 4 neutropenia with SIR was not associated with infections. Disclosure of Interest T. Takeuchi Grant/research support from: Astellas Pharma, Bristol-Myers K.K., Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Eisai Co., Ltd., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., Santen Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Teijin Pharma Ltd., AbbVie GK, Asahi Kasei Pharma Corp., Taisho Toyama Pharmaceutical Co., Ltd., and SymBio Pharmaceuticals Ltd, Consultant for: Astra Zeneca K.K., Eli Lilly Japan K.K., Novartis Pharma K.K., Mitsubishi Tanabe Pharma Co., Asahi Kasei Medical K.K., AbbVie GK, Daiichi Sankyo Co., Ltd., Bristol-Myers K.K., and Nipponkayaku Co. Ltd., Speakers bureau: AbbVie GK., Bristol-Myers K.K., Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., Takeda Pharmaceutical Co., Ltd., Astellas Pharma, Daiichi Sankyo Co., Ltd., Celtrion, and Nipponkayaku Co. Ltd., Y. Tanaka Grant/research support from: Mitsubishi-Tanabe, Takeda, Daiichi-Sankyo, Chugai, Bristol-Myers, MSD, Astellas, Abbvie, and Eisai, Speakers bureau: Abbvie, Chugai, Daiichi-Sankyo, Bristol-Myers, Mitsubishi-Tanabe, Astellas, Takeda, Pfizer, Teijin, Asahi-kasei, YL Biologics, Sanofi, Janssen, Eli Lilly, and GlaxoSmithKline, M. Schiff Consultant for: AbbVie, Bristol-Myers Squibb, Eli Lilly, Johnson & Johnson, UCB, Speakers bureau: AbbVie, M. Harigai Grant/research support from: AbbVie Japan, Astellas Pharma, Bristol-Myers Squibb, Chugai Pharmaceutical, Eisai, Mitsubishi Tanabe Pharma, Ono Pharmaceuticals, Santen Pharmaceutical, Takeda Pharmaceutical, UCB Japan, Teijin Pharma, Consultant for: AbbVie Japan, Janssen Pharma, Chugai Pharmaceutical, Teijin Pharma, Eli Lilly Japan, and Zenyaku Kogyo, K. Brown Shareholder of: GlaxoSmithKline, Employee of: GlaxoSmithKline, R. Rao Shareholder of: GlaxoSmithKline, Employee of: GlaxoSmithKline, K. Fei Shareholder of: Janssen Research & Development, LLC, Employee of: Janssen Research & Development, LLC, S. Popik Shareholder of: Janssen Research & Development, LLC, Employee of: Janssen Research & Development, LLC, K. Yoshizawa Shareholder of: Janssen Research & Development, LLC, Employee of: Janssen Research & Development, LLC, Q. Wang Shareholder of: Janssen Research & Development, LLC, Employee of: Janssen Research & Development, LLC, B. Hsu Shareholder of: Janssen Research & Development, LLC, Employee of: Janssen Research & Development, LLC

Distigmine bromide (distigmine) is a reversible carbamate group cholinesterase (ChE) inhibitor. Although mainly used clinically for the treatment of myasthenia gravis, distigmine is also indicated for detrusor underactivity in Japan. According to the pharmacological classification of distigmine, its therapeutic effect against detrusor underactivity appears to be produced by enhanced urinary bladder smooth muscle (UBSM) contractility due to an increased concentration of acetylcholine between parasympathetic nerve endings and UBSM cells. However, ATP as well as acetylcholine is also released from parasympathetic nerve endings that dominate UBSM. The present study was thus carried out to investigate the potentiating effects of distigmine on the two UBSM contractile components in response to parasympathetic nerve stimulation induced by electrical field stimulation (EFS). In isolated guinea pig UBSM tissues, EFS (1-16Hz) produced tetrodotoxin-sensitive, frequency-dependent contractions. The contractile responses to EFS were largely diminished by atropine (10-6M), and the remaining contractile components in the presence of atropine were virtually abolished by α,β-methylene adenosine triphosphate (α,β-mATP) (10-4M). Distigmine (10-6M) significantly potentiated EFS-induced contractile components generated in the presence of α,β-mATP (10-4M), but did not potentiate EFS-induced contractile components generated in the presence of atropine (10-6M). These findings clearly indicate that distigmine strongly potentiates UBSM contraction selectively induced by parasympathetic nerve-derived acetylcholine, suggesting a potential mechanism by which distigmine restores detrusor underactivity.

Objective The present study elucidates whether or not preserving fat tissues deeper than the Scarpa's fascia in zone 3 and zone 4 reduces postoperative fluid collection after harvesting the transverse rectus-abdominis muscle (TRAM) flap. Methods Thirty-one patients for whom breast reconstruction with free TRAM flaps had been performed were included in the study. Fat tissues deeper than the Scarpa's fascia in zone 3 and zone 4 were addressed in two ways. With 17 patients, these tissues were preserved on the abdominal wall; with 14 patients, these fat tissues were harvested as part of the TRAM flap. The former and latter groups were named the Preservation Group and Non-Preservation Group, respectively. Drainage tubes were placed at the donor site until daily drainage became less than 20 ml, at which time the tubes were removed. The total amount of postoperative fluid drained from the donor site and the days required before tube removal were compared between the two groups. Results The total volume of drained fluid was significantly greater for the Non-Preservation Group (444 ± 48.2 ml) than for the Preservation Group (230 ± 21.9 ml); the period before removal of drainage tubes was significantly longer for the Non-Preservation Group (12.4 ± 0.84 days) than for the Preservation Group (7.6 ± 0.55 days). Conclusion Preservation of deep-fat tissues in zone 3 and zone 4 reduces postoperative fluid exuded from the donor site, and enables earlier removal of drainage tubes. For cases where optimal breast shape can be achieved without these fat tissues, the fat tissues should be preserved.

Background/Aims: Effects of docosahexaenoic acid (DHA) on blood vessel contractions to various constrictors were investigated in rat mesenteric artery and compared with those of eicosapentaenoic acid (EPA) and linoleic acid (LA). Methods: Tension changes in mesenteric ring segments were isometrically recorded. Results: On sustained contractions induced by a thromboxane A2 mimetic (U46619), DHA exerted a strong inhibitory effect. This inhibitory effect of DHA on U46619 appeared both in endothelium-intact and endothelium-denuded preparations. Although the inhibitory effect of DHA on prostaglandin F2α (PGF2α)-induced contractions was also significant, contractions to phenylephrine (PE) and high-KCI were not affected by DHA. As well as DHA, EPA strongly diminished U46619- and PGF2α-induced contractions without showing a substantial inhibition of PE- and high-KCl-induced contractions. By contrast, LA did not show any significant inhibitory effects on any contractions. The DHA-induced inhibitory actions exerted on U46619 and PGF2α also emerged if ring preparations were pretreated with this ω-3 polyunsaturated fatty acid (PUFA). Conclusion: DHA and EPA are found to more pronouncedly inhibit prostanoid receptor-mediated contractions than other constrictor responses of the mesenteric artery via endothelium-independent mechanisms. These inhibitory effects of ω-3 PUFAs on prostanoid receptor-mediated contractions may partly underlie the mechanisms by which these ω-3 PUFAs elicit protective actions against circulatory disorders.

Sludge-like uranium-bearing wastes generated from uranium refining and conversion R&D facilities are stored at the Ningyo-toge Environmental Engineering Center of the Japan Atomic Energy Agency. So...

This journal suppl. entitled: Special Issue: The 64th Annual Meeting of the American Association for the Study of Liver Diseases: The Liver Meeting 2013

Atualmente, a competitividade do mercado exige que as organizações busquem melhorias em seus processos e o OEE (Overall Equipment Effectiveness) tornou-se uma ferramenta importante na busca da eficiência do processo quando combinado com outras tecnologias. Este estudo teve como objetivo investigar o efeito do monitoramento do OEE em tempo real no processo de tomada de decisão em uma empresa. Utilizou-se de uma pesquisa exploratória e o um estudo de caso de uma empresa de fabricação de brinquedos, onde se verificou que a adoção do sistema de monitoramento em tempo real foi importante para a melhoria na tomada de decisões, pois permitiu o monitoramento rápido e dinâmico, bem como a possibilidade de priorizar melhorias nos processos de produção.

Recently, one of the rare sugars, D-allose, has received attention from many researchers because of its availability for mass production and its various physiological functions. Among these, an antioxidative effect has been strongly suggested. In this study, we investigated whether this effect is also applicable to the field of skin surgery.In ischemia-reperfusion injury model using the rat abdominal skin island flap (male Wistar rats, n = 110), D-allose was injected intravenously 15 min before 8-h ischemia. The survival area (%) was measured by digital photographic assessment 1 wk after surgery, and multiple comparisons (Fisher's protected least significant difference) were carried out. Histopathological examination (neutrophilic infiltration into dermis in hematoxylin and eosin stain) and immunostaining (of ectodermal dysplasia-1 (ED1)-positive cells/flap) were assessed. Myeloperoxidase (MPO) activity in the skin flap (sampling at the time of 8 h after reperfusion) was measured spectrophotometrically, and Student t-test was performed.D-allose extended the survival of the remaining flaps, and a dose greater than 30 mg (0.1 mg/g) was necessary to be effective. The flap survival rates in the 30, 60, and 150 mg groups were significantly higher than that in the control (saline) group: 75.87 ± 5.90, 79.27 ± 7.81, and 77.87 ± 6.20 versus 50.53 ± 9.66, respectively (P0.05). ED1-positive cells/flap in 60 mg of D-allose and control (saline) were 78 ± 25.7 versus 124 ± 15.8, respectively (P = 0.08). The MPO activity in the D-allose 60 mg group was 0.40 ± 0.04, and that in the control (saline) was 0.72 ± 0.12. D-allose significantly reduced the skin tissue MPO activity (P0.05) compared with that in the control (saline) group.We proved that D-allose has a reducing effect against ischemia-reperfusion injury on the skin island flap model, and the mechanism is related to inhibiting the activity of neutrophils in the skin tissues. Compared with chemo-synthetic materials, rare sugars are safer for our bodies as well as the environment; therefore, this rare sugar project is expected to lead to the development of a safer antioxidant for skin flap surgery.

The purpose of this study was to investigate whether there is a risk of thrombosis in the temporary arteriovenous shunt loop (TAVSL). The authors established a TAVSL model in the rabbit. Experimental groups were divided into non-heparin treated and heparin treated. The maximum blood flow volume, blood viscosity, and radius of curvature were measured, and the Reynolds number and the sheer stress were calculated. Computational fluid dynamics (CFD) was used to predict the flow pattern in the TAVSL, and these predicted data were compared with histological results. Early occlusion was noted in 70% (7/10) of the non-heparin-treated group and 22% (2/9) of the heparin-treated group. CFD analysis predicted a high shear stress at the arterial anastomosis region and the outer luminal surface of the curved section. The intimal structure at the luminal surface of the curved section was extensively lost histologically. In the patent group, severe stenosis of the lumen was noted at the apex of the loop due to an organized thrombus. Thus, thrombosis is likely to occur in the TAVSL due to endothelium injury caused by high shear stress, and this results in the formation of white thrombi at an early stage and an organized thrombus at a late stage.

Review: An increased number of rescuers may improve the survival rate from out-of-hospital cardiac arrests (OHCAs). The majority of OHCAs occur at home and are handled by family members. Materials and methods: Data from 5078 OHCAs that were witnessed by citizens and unwitnessed by citizens or emergency medical technicians from January 2004 to March 2010 were prospectively collected. The number of rescuers was identified in 4338 OHCAs and was classified into two (single rescuer (N = 2468) and multiple rescuers (N = 1870)) or three (single rescuer, two rescuers (N = 887) and three or more rescuers (N = 983)) groups. The backgrounds, characteristics and outcomes of OHCAs were compared between the two groups and among the three groups. Results: When all OHCAs were collectively analysed, an increased number of rescuers was associated with better outcomes (one-year survival and one-year survival with favourable neurological outcomes were 3.1% and 1.9% for single rescuers, 4.1% and 2.0% for two rescuers, and 6.0% and 4.6% for three or more rescuers, respectively (p = 0.0006 and p < 0.0001)). A multiple logistic regression analysis showed that the presence of multiple rescuers is an independent factor that is associated with one-year survival (odds ratio (95% confidence interval): 1.539 (1.088-2.183)). When only OHCAs that occurred at home were analysed (N = 2902), the OHCAs that were handled by multiple rescuers were associated with higher incidences of bystander CPR but were not associated with better outcomes. Conclusions: In summary, an increased number of rescuers improves the outcomes of OHCAs. However, this beneficial effect is absent in OHCAs that occur at home. © 2012 Elsevier Ireland Ltd. All rights reserved.

Inhibitory effects of docosahexaenoic acid (DHA) on blood vessel contractions induced by various constrictor stimulants were investigated in the rat thoracic aorta. The inhibitory effects of DHA were also compared with those of eicosapentaenoic acid (EPA) and linoleic acid (LA). DHA exhibited a strong inhibitory effect on the sustained contractions induced by U46619, a TXA(2) mimetic. This inhibitory effect of DHA was not affected by removal of the endothelium or by treatment with either indomethacin or N(ω)-nitro-l-arginine. DHA also significantly diminished PGF(2α)-induced contraction but did not show any appreciable inhibitory effects on the contractions to both phenylephrine (PE) and high-KCl. Similarly, EPA exhibited significant inhibitory effects against the contractions induced by both U46619 and PGF(2α) without substantially affecting either PE- or high-KCl-induced contractions. However, both DHA and EPA generated more potent inhibitions against contractions induced by U46619 than those by PGF(2α). In contrast, LA did not show significant inhibitory effects against any contractions, including those induced by U46619. The present findings suggest that DHA and EPA elicit more selective inhibition against blood vessel contractions that are mediated through stimulation of prostanoid receptors than those through α-adrenoceptor stimulation or membrane depolarization. Although DHA and EPA have similar inhibitory potencies against prostanoid receptor-mediated contractions, they had a more potent inhibition against TXA(2) receptor (TP receptor)-mediated contractions than against PGF(2α) receptor (FP receptor)-mediated responses. Selective inhibition by either DHA or EPA of prostanoid receptor-mediated blood vessel contractions may partly underlie the mechanisms by which these ω-3 polyunsaturated fatty acids exert their circulatory-protective effects.

SUMMARY A virtual machine (VM) migration is useful for improving flexibility and maintainability in cloud computing environments. However, VM monitor (VMM)-bypass I/O technologies, including PCI passthrough and SR-IOV, in which the overhead of I/O virtualization can be significantly reduced, make VM migration impossible. This paper proposes a novel and practical mechanism, called Symbiotic Virtualization (SymVirt), for enabling migration and checkpoint/restart on a virtualized cluster with VMM-bypass I/O devices, without the virtualization overhead during normal operations. SymVirt allows a VMM to cooperate with a message passing layer on the guest OS, then it realizes VM-level migration and checkpoint/restart by using a combination of a user-level dynamic device configuration and coordination of distributed VMMs. We have implemented the proposed mechanism on top of QEMU/KVM and the Open MPI system. All PCI devices, including Infiniband, Ethernet, and Myrinet, are supported without implementing specific para-virtualized drivers; and it is not necessary to modify either of the MPI runtime and applications. Using the proposed mechanism, we demonstrate reactive and proactive FT mechanisms on a virtualized Infiniband cluster. We have confirmed the effectiveness using both a memory intensive micro benchmark and the NAS

Review: In 2007, the Ishikawa Medical Control Council initiated the continuous quality improvement (CQI) project for telephone-assisted cardiopulmonary resuscitation (telephone-CPR), which included instruction on chest-compression-only CPR, education on how to recognise out-of-hospital cardiac arrests (OHCAs) with agonal breathing, emesis and convulsion, recommendations for on-line or redialling instructions and feedback from emergency physicians. This study aimed to investigate the effect of this project on the incidence of bystander CPR and the outcomes of OHCAs. Materials and methods: The baseline data were prospectively collected on 4995 resuscitation-attempted OHCAs, which were recognised or witnessed by citizens rather than emergency medical technicians during the period of February 2004 to March 2010. The incidence of telephone-CPR and bystander CPR, as well as the outcomes of the OHCAs, was compared before and after the project. Results: The incidence of telephone-CPR and bystander CPR significantly increased after the project (from 42% to 62% and from 41% to 56%, respectively). The incidence of failed telephone-CPR due to human factors significantly decreased from 30% to 16%. The outcomes of OHCAs significantly improved after the projects. A multiple logistic regression analysis revealed that the CQI project is one of the independent factors associated with one-year (1-Y) survival with favourable neurological outcomes (odds ratio = 1.81, 95% confidence interval = 1.20-2.76). Conclusions: The CQI project for telephone-CPR increased the incidence of bystander CPR and improved the outcome of OHCAs. A CQI project appeared to be essential to augment the effects of telephone-CPR. © 2012 Elsevier Ireland Ltd. All rights reserved.

Background/Aims: To investigate the potential inhibitory effects of 18 clinically available antidepressants on acetylcholine (ACh)-induced contractions in guinea pig urinary bladder smooth muscle (UBSM) in order to predict whether they may induce voiding impairment. Methods: Concentration-response curves for ACh-induced contractions in guinea pig UBSM strips were obtained in the absence or presence of selected antidepressants. When inhibitory effects indicated competitive antagonism, pA2 values against ACh were calculated and compared to plausible antidepressant blood concentrations. Results: ACh-induced contraction was antagonized competitively within clinical dose ranges by tricyclic antidepressants (imipramine, amitriptyline, trimipramine, clomipramine, nortriptyline, and amoxapine), maprotiline (a tetracyclic antidepressant), and mirtazapine (a noradrenergic and specific serotonergic antidepressant). ACh-induced contraction was also significantly inhibited by mianserin (a tetracyclic antidepressant), paroxetine and sertraline (serotonin-selective reuptake inhibitors, SSRIs), and duloxetine (a serotonin noradrenaline (norepinephrine) reuptake inhibitor, SNRI), albeit at concentrations that substantially exceeded clinically achievable blood levels. However, ACh-induced contractions were not significantly affected by fluvoxamine and escitalopram (SSRIs), milnacipran (an SNRI), trazodone (a serotonin 5-HT2A receptor antagonist), sulpiride (a dopamine D2 receptor antagonist), or aripiprazole (a dopamine partial agonist). Conclusion: These findings suggest that in addition to tricyclics, some relatively novel antidepressants such as mirtazapine can induce voiding impairment, attributed to diminished UBSM contractility from the inhibition of muscarinic receptors in the UBSM.

Sludge-like uranium wastes (SUWs) have been generated with neutralization of acidic aqueous solutions used for decontamination of metal wastes containing a large amount of iron. We have examined the method for recovering uranium from such SUWs using N-cyclohexyl-2-pyrrolidone (NCP) as a precipitate. As a result, it was found that precipitation ratios (PRs) of uranium in the solutions prepared by dissolving SUWs in HNO3 increase with increasing an amount of added NCP and are 97.7% at [NCP]/[U(VI)] = 20, and that the PRs of iron, aluminum, fluorine, and sulfate species are less than 1% at [NCP]/[U(VI)] = 3–20. This indicates that uranium species are precipitated selectively. The content ratios of U, Fe, Ca, F, and S in the materials after calcining precipitates obtained at [NCP]/[U(VI)] = 20 were 73, 2.2 × 10−1, −3, 2.3 × 10−2, and 2.2 × 10−2 wt%, respectively. These values are in accordance with the conditions of uranium ore concentrate defined by ConverDyn Corp and ASTM C967. From these results, it is expected that highly purified uranium can be efficiently recovered from SUWs by using NCP as the precipitant.

There are many studies on spatial distributions of Asari clam Ruditapes philippinarum adults on tidal flats but few have dealt with spatial distributions of newly settled Asari clam (

Plan the use of factors related to the implementation of continuous improvement projects increases the potential for success and effectiveness of them. The objective of this paper is to analyze factors for the implementation of projects in the shop floor environment. This research involves perspectives of consultants and project leaders in different organizations. It is qualitative research and has two steps of data collection: (a) interviews (semi-structured questionnaires) with consultants and improvements project leaders in industries from various sectors (agricultural chemicals, automotive, machining, stamping and aerospace) and (b) questionnaire in three plants of a large chemical group with a tradition of research and development. This study is delimited to industrial and consulting firm specializing in continuous improvement projects. Critical factors as top management commitment, leadership, projects aligned with business goals, culture of continuous improvement, goals, leader’s behaviour highlighted.

Although similarity of pharmacological responses to certain stimuli between guinea pigs and humans has been reported, this has been poorly defined by a molecular biological approach. In this study, we cloned the gene of guinea pig ?1-adrenoceptor (ADRB1). The deduced amino acid sequence of guinea pig ADRB1 (467-aa) showed 91% and 92% identity with the human and rat ADRB1 sequences, respectively. Using HEK293T cells expressing guinea pig, human and rat ADRB1s independently, we elucidated the functional characteristics of each ADRB1. The ligand-binding profiles and the concentration-response relationships for isoprenaline-induced cyclic adenosine monophosphate (cAMP) production were similar among the three ADRB1s. Isoprenaline also induced phosphorylation of extracellular-signal related kinases (ERK) through ADRB1s in a concentration-dependent manner. The minimum effective concentration of isoprenaline for phosphorylation of ERK, through guinea pig ADRB1 was the same as through human ADRB1, but markedly lower than that of through rat ADRB1. ERK phosphorylation through guinea pig ADRB1 was sensitive to pertussis toxin, a dominant-negative ras and PD98059, indicating that a G(i)-mediated pathway is involved in the ADRB1/ERK signaling loop. These results suggest that the G(i)-coupling efficacy of guinea pig and human ADRB1s may be higher than that of rat ADRB1.

SummaryIn most stem cell systems, the organization of the stem cell niche and the anchoring matrix required for stem cell maintenance are largely unknown. We report here that collagen XVII (COL17A1/BP180/BPAG2), a hemidesmosomal transmembrane collagen, is highly expressed in hair follicle stem cells (HFSCs) and is required for the maintenance not only of HFSCs but also of melanocyte stem cells (MSCs), which do not express Col17a1 but directly adhere to HFSCs. Mice lacking Col17a1 show premature hair graying and hair loss. Analysis of Col17a1-null mice revealed that COL17A1 is critical for the self-renewal of HFSCs through maintaining their quiescence and immaturity, potentially explaining the mechanism underlying hair loss in human COL17A1 deficiency. Moreover, forced expression of COL17A1 in basal keratinocytes, including HFSCs, in Col17a1-null mice rescues MSCs from premature differentiation and restores TGF-β signaling, demonstrating that HFSCs function as a critical regulatory component of the MSC niche.

The high-performance Geospatial Information System (GIS) is expected to provide an innovative infrastructure for Earth sciences, enabling near-real-time data and processing services. Stereo-matching software has often been used in generating a Digital Elevation Model (DEM) from a pair of satellite imagery data sets to compute height from a parallax views using two photographic images. There is a need to reduce the computation time required for processing large images. We optimize stereo-matching software on multi-core/many-core processors, including Xeon, Cell and GPGPU. We describe optimization approaches of the correlation calculation part which occupied about 55% of the ovarall computation time. After porting and optimizing software for multi-core/many-core processors, we achieved processing time of 4.79 second (Xeon), 2.28 second (Cell) and 0.97 second (GPGPU) on each platform.