Propensity score analysis comparing off-pump versus on-pump coronary artery bypass grafting in older adults.

OBJECTIVE: This study aimed to compare the results of off-pump and on-pump coronary artery bypass grafting in older adults and to examine early and late outcomes. METHODS: This study included 226 patients aged ≥ 75 years who underwent isolated coronary artery bypass grafting. Of these, 141 and 85 patients were included in the off-pump and on-pump groups, respectively. Propensity scores were calculated for each case, matched, and compared between the two groups (68 cases in each group), along with mid-term outcomes of survival and major adverse cardiac events. RESULTS: Operative time, red blood cell transfusion volume, and postoperative hospital stay duration were significantly higher in the on-pump group (267 vs 370 min, P < 0.001; 4.3 vs 17.2 units, P < 0.001; and 20.8 vs 35.8 days, P = 0.012, respectively). Postoperative occurrence of new atrial fibrillation was significantly higher in the on-pump group (4.4% vs 27.9%, P < 0.001), and Kaplan-Meier survival analysis showed a significantly worse prognosis in the on-pump group than in the off-pump group (3-year survival rate 90.7% vs 71.5%, log rank P = 0.007). However, there was no statistically significant difference in cardiovascular-related deaths (log rank P = 0.07). CONCLUSIONS: On-pump coronary artery bypass grafting in an older adult population resulted in increased transfusion volume and postoperative occurrence of atrial fibrillation. The mid-term postoperative outcomes were also poorer with on-pump coronary artery bypass grafting. Off-pump coronary artery bypass grafting reduced future all-cause deaths in older adults.

Single-stage repair for ascending aortic aneurysm, artery stenosis and occlusion of neck vessels caused by Takayasu arteritis.

Takayasu arteritis results in a variety of vascular symptoms, and there are some cases in which progressive vascular lesions require surgical intervention. We present a case with ascending aortic aneurysm, right common carotid artery stenosis, left common carotid artery occlusion and left subclavian artery stenosis caused by Takayasu arteritis that was successfully treated with total arch replacement and ascending aorta to right internal carotid artery bypass.

Successful management of segmental zoster paresis on the upper arm with temporally burst spinal cord stimulation.

Segmental zoster paresis (SZP) of the limbs is characterized by a focal, asymmetric neurogenic weakness that may occur in an extremity affected by herpes zoster (HZ). In this case report, we describe the case of a patient with SZP who presented with these problems and responded well to temporary spinal cord stimulation (SCS) and systematic rehabilitation. A 62-year-old female patient was referred for right upper limb pain, weakness, and insomnia due to pain. After completing the 14-day trial stimulation, the pain numerical rating scale of the patient in the right upper extremity decreased from 8/10 to 2/10. The Athens insomnia scale score decreased from 15/24 to 10/24. Furthermore, the grip strength of the right hands increased from 6.7 to 16.8 kg at discharge. We induced temporal SCS and rehabilitation of the right upper limb SZP and successfully reduced the pain. An in-depth understanding of the neurological complications secondary to HZ should be emphasized, with temporal SCS and rehabilitation expected to play a crucial role in the motor recovery of patients with SZP.

Application of the Sinter-HIP Method to Manufacture Cr-Mo-W-V-Co High-Speed Steel via Powder Metallurgy.

1.2C-4Cr-4Mo-10W-3.5V-10Co-Fe high-speed steel (JIS SKH57; ISO HS10-4-3-10) is often manufactured via casting and forging. By applying powder metallurgy, the properties of the abovementioned material can be improved. In this study, the effects of sintering conditions on the formation of precipitates and pores are evaluated. Additionally, strength with and without hydrostatic pressure during sintering is evaluated via static bending and impact tests. Sintering via hot isostatic pressing (HIP) at 1463 K can effectively eliminate pores and prevent the coarsening of precipitates. Toughness and strength improved by 50% by applying HIP.

Association between myotonometric measurement of masseter muscle stiffness and maximum bite force in healthy elders.

BACKGROUND: Maximum bite force (MBF) is a common and useful index of masticatory function; it correlates with physical strength in elderly people. Palpation of stiffness in the masseter muscle during forceful biting has been considered to be associated with MBF. However, this assessment method relies on subjective judgments; no study has verified the relationship between MBF and quantitative measurements of masseter muscle stiffness (MMS). OBJECTIVE: We aimed to verify the association between masseter muscle myotonometric assessment results and MBF. METHODS: In total, 117 community-dwelling >65-year-old individuals from the Tokyo metropolitan area were assessed. MMS on the dominant side during forceful biting was measured with a MyotonPRO device. Masseter muscle thickness (MMT) during rest and forceful biting was measured with an ultrasonic diagnostic apparatus, and the difference in MMT (DMMT) between the rest and forceful biting conditions was determined. MBF data were obtained with a pressure-sensitive sheet and an associated device. To determine the independent variables affecting MBF and MMS, multivariate linear regression analyses with adjustments for age, sex and number of teeth were performed. RESULTS: The multivariate analysis revealed that MBF correlated with the number of teeth (ß = .489, P < .001) and MMS (ß = .259, P = .003) (R2  = .433). MMS correlated with MBF (ß = .308, P = .003) and DMMT (ß = .430, P < .001) (R2  = .326). CONCLUSION: Masseter muscle stiffness possibly reflects a force generated by the masseter muscle during forceful biting. Therefore, MMS is effective to assess tooth loss as well as an index of masseter muscle strength when evaluating MBF.

Relationship between displacement of the masseter muscle during biting and masseter muscle quality and bite force in healthy elderly persons.

BACKGROUND: Although age-related changes in muscle quality influence muscle strength, the relationship between masseter muscle (MM) quality and maximum biting force (MBF) has never been studied. OBJECTIVE: The aims of the study were to verify the relationship among MM quality, MBF, and the displacement of the MM while biting forcefully (MMD) and to clarify the age-related decline in MBF in healthy elderly persons. METHODS: Seventy-four healthy community-dwelling individuals (mean age, >65 years) from Tokyo metropolis were recruited. The thickness (index of muscle quantity), echo intensity (index of muscle quality) and displacement of the MM while biting forcefully (MMT, MMEI and MMD, respectively) were measured by ultrasonography. MBF was measured using a pressure-sensitive sheet. Independent predictors of MBF and MMD were determined using multivariate linear regression analyses adjusted for age, sex and the number of present teeth. RESULTS: MBF was significantly correlated with the number of teeth (ß = 0.577, P < .001) and MMD (ß = 0.302, P = .015), but not with MMT (ß = 0.019, P = .868) or MMEI (ß = 0.054 P = .703). MMD was significantly correlated with MMEI (ß = -0.606, P < .001), but not with MMT (ß = 0.048, P = .681) or the number of teeth (ß = 0.065, P = .613). CONCLUSIONS: MMEI was associated with MMD, an index of MBF, regardless of tooth number. The age-related quality change in the MM might cause a decrease in its contraction, resulting in age-related decline in MBF.

Analyses of natural courses of Japanese patients with Alzheimer's disease using placebo data from placebo-controlled, randomized clinical trials: Japanese Study on the Estimation of Clinical course of Alzheimer's disease.

INTRODUCTION: Symptomatic anti-Alzheimer's disease (AD) drugs have been commonly used for the treatment of AD. Knowing the natural courses of patients with AD on placebo is highly relevant for clinicians to understand their efficacy and for investigators to design clinical studies. METHODS: The data on rating scales for dementia such as Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) and Severe Impairment Battery were extracted from eight previous Japanese Phase II and III studies. Natural courses of Japanese AD patients in placebo groups were evaluated and statistically analyzed in a pooled and retrospective fashion. RESULTS: Decreases in ADAS-cog and Severe Impairment Battery was larger at week 22 or 24 than at week 12. Scores of ADAS-cog appeared to deteriorate faster in moderate AD than in mild AD. DISCUSSION: The present data will provide clinicians following up patients with AD with helpful information on how to manage AD patients and investigators with instruction for clinical study design.

Synthesis of Amide and Ester Derivatives of Cinnamic Acid and Its Analogs: Evaluation of Their Free Radical Scavenging and Monoamine Oxidase and Cholinesterase Inhibitory Activities.

A series of cinnamic acid derivatives, amides (1-12) and esters (13-22), were synthesized, and structure-activity relationships for antioxidant activity, and monoamine oxidases (MAO) A and B, acetylcholinesterase, and butyrylcholinesterase (BChE) inhibitory activities were analyzed. Among the synthesized compounds, compounds 1-10, 12-18, and rosmarinic acid (23), which contained catechol, o-methoxyphenol or 5-hydroxyindole moieties, showed potent 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging activity. Compounds 9-11, 15, 17-22 showed potent and selective MAO-B inhibitory activity. Compound 20 was the most potent inhibitor of MAO-B. Compounds 18 and 21 showed moderate BChE inhibitory activity. In addition, compound 18 showed potent antioxidant activity and MAO-B inhibitory activity. In a comparison of the cinnamic acid amides and esters, the amides exhibited more potent DPPH free radical scavenging activity, while the esters showed stronger inhibitory activities against MAO-B and BChE. These results suggested that cinnamic acid derivatives such as compound 18, p-coumaric acid 3,4-dihydroxyphenethyl ester, and compound 20, p-coumaric acid phenethyl ester, may serve as lead compounds for the development of novel MAO-B inhibitors and candidate lead compounds for the prevention or treatment of Alzheimer's disease.

Long non-coding RNA MALAT1 is an inducible stress response gene associated with extramedullary spread and poor prognosis of multiple myeloma.

Extramedullary myeloma (EMM) occurs when myeloma develops outside the bone marrow; it often develops after chemotherapy and is associated with the acquisition of chemo-resistance and a fatal course. The mechanisms underlying extramedullary spread have not yet been fully elucidated. MALAT1 is a highly abundantly and ubiquitously expressed long non-coding RNA that plays important roles in cancer metastasis. The aims of this study were to clarify the association of MALAT1 with EMM and to elucidate the underlying mechanism of EMM formation under chemotherapeutic pressure. MALAT1 expression was significantly higher in multiple myeloma (MM) than in monoclonal gammopathy of undetermined significance. Furthermore, MALAT1 expression was markedly higher in EMM compared with that in corresponding intramedullary myeloma cells. A higher MALAT1 level was associated with shorter overall and progression-free survival. MALAT1 expression level was positively correlated with expression of HSP90AA1, HSP90AB1 and HSP90B1 but not with TP53 expression. MALAT1 was significantly upregulated by bortezomib and doxorubicin. Considering the known functions of MALAT1, our results suggest that it acts as a stress response gene that is upregulated by chemotherapy, thereby linking chemotherapy to EMM formation. Elucidating the biological implication of long non-coding RNA contributes to deeper understanding concerning the pathogenesis and investigation of novel therapeutic targets for MM.

2-Azolylchromone Derivatives as Potent and Selective Inhibitors of Monoamine Oxidases A and B.

A series of 2-azolylchromone derivatives were synthesized and their monoamine oxidase (MAO) A and B inhibitory activities were evaluated. Of the synthesized compounds, compounds 1b, 2b, 4a-c, 5b and 7b showed potent inhibitory activities against MAO-A (IC50 values, 1b: 0.32 µM; 2b: 0.14 µM; 4a: 0.11 µM; 4b: 0.023 µM; 4c: 0.15 µM; 5b: 0.59 µM; 7b: 0.19 µM) and 4a, c, 5a, c, 6c and 8c for MAO-B (IC50 values, 4a: 0.028 µM; 4c: 0.019 µM; 5a: 0.73 µM; 5c: 0.28 µM; 6c: 0.28 µM; 8c: 0.27 µM). These data suggest that 6-methoxy substitution favors MAO-A inhibition and 7-methoxy substitution favors MAO-B inhibition. In addition, compound 4b was the most potent inhibitor for MAO-A, and compound 4c for MAO-B. This is the first report identifying 2-azolylchromone derivatives as potent monoamine oxidase inhibitors. These results suggest that the 2-triazolylchromone structure may be a useful scaffold for the design and development of novel monoamine oxidase inhibitors, as evidenced by the activities of 4a-c and 5a-c.

Peripheral Nerve Block Facilitates Acute Inflammatory Responses Induced by Surgical Incision in Mice.

BACKGROUND AND OBJECTIVES: Anesthesia with peripheral nerve block (PNB) improves the early recovery profile of patients undergoing surgery, including the control of postoperative pain, opioid consumption, and the length of hospital stay. However, the influence of PNB on wound inflammation and the repair process has not been fully investigated. Therefore, we evaluated the effects of PNB on local inflammation of incised tissue in the acute phase of postoperative pain development. METHODS: Sciatic nerve block with 0.5% ropivacaine was performed before plantar incision in mice. Pain behavior, neutrophil infiltration, phagocytosis of apoptotic cells, and gene induction of inflammatory mediators were assessed for 7 days postoperatively. RESULTS: Sciatic nerve block with 0.5% ropivacaine treatment transiently increased the withdrawal threshold to mechanical stimuli and thermal latency for 2 hours after surgical incision, whereas no changes were observed from 3 hours after incision throughout the postoperative period. However, Gr-1 neutrophil infiltration and the number of CD68 macrophages engulfing TdT-mediated dUTP nick-end labeling apoptotic cells were significantly increased after incision. Tumor necrosis factor α and prostaglandin E2 were up-regulated at the incised sites. In addition, the expressions of lipoxygenase-15 and heme oxygenase-1, which resolve inflammation and promote wound healing after the acute inflammatory phase, were increased. CONCLUSIONS: Single PNB before incision promoted acute phase inflammation mediated by neutrophils and macrophages at the sites of incision, whereas postoperative pain was not altered. Peripheral nerve block might locally accelerate innate immune responses after surgical incision without altering the nociceptive profile.

Visualization of Uptake of Mineral Elements and the Dynamics of Photosynthates in Arabidopsis by a Newly Developed Real-Time Radioisotope Imaging System (RRIS).

Minerals and photosynthates are essential for many plant processes, but their imaging in live plants is difficult. We have developed a method for their live imaging in Arabidopsis using a real-time radioisotope imaging system. When each radioisotope,(22)Na,(28)Mg,(32)P-phosphate,(35)S-sulfate,(42)K,(45)Ca,(54)Mn and(137)Cs, was employed as an ion tracer, ion movement from root to shoot over 24 h was clearly observed. The movements of(22)Na,(42)K,(32)P,(35)S and(137)Cs were fast so that they spread to the tip of stems. In contrast, high accumulation of(28)Mg,(45)Ca and(54)Mn was found in the basal part of the main stem. Based on this time-course analysis, the velocity of ion movement in the main stem was calculated, and found to be fastest for S and K among the ions we tested in this study. Furthermore, application of a heat-girdling treatment allowed determination of individual ion movement via xylem flow alone, excluding phloem flow, within the main stem of 43-day-old Arabidopsis inflorescences. We also successfully developed a new system for visualizing photosynthates using labeled carbon dioxide,(14)CO2 Using this system, the switching of source/sink organs and phloem flow direction could be monitored in parts of whole shoots and over time. In roots,(14)C photosynthates accumulated intensively in the growing root tip area, 200-800 µm behind the meristem. These results show that this real-time radioisotope imaging system allows visualization of many nuclides over a long time-course and thus constitutes a powerful tool for the analysis of various physiological phenomena.

Myeloperoxidase negatively regulates the expression of proinflammatory cytokines and chemokines by zymosan-induced mouse neutrophils.

OBJECTIVE: We have previously reported that myeloperoxidase-deficient (MPO(-/-)) neutrophils produce greater amounts of macrophage inflammatory protein-2 (MIP-2) upon in vitro stimulation with zymosan than wild-type neutrophils. This study aimed to examine the effect of MPO deficiency on the expression of other cytokines and chemokines. METHODS: Wild-type and MPO(-/-) neutrophils isolated from peritoneal cavity were stimulated with zymosan in vitro. Secretion of MIP-1α, MIP-1ß, interleukin (IL)-1α, IL-1ß, and tumor necrosis factor (TNF)-α by neutrophils was quantified by ELISA. mRNA expression in the neutrophils was analyzed by real-time reverse transcription-PCR, and the phosphorylation of extracellular-signal regulated kinase (ERK) 1/2 and p38 mitogen activated protein kinase (MAPK) in neutrophils was analyzed by western blot. For in vivo studies, mice were inoculated with zymosan intranasally, and the levels of these cytokines and chemokines were measured in the lungs. RESULTS: The MPO(-/-) neutrophils stimulated by zymosan expressed and secreted significantly higher levels of MIP-1α, MIP-1ß, IL-1α, IL-1ß, and TNF-α than the stimulated wild-type cells. Expression of all of these inflammatory mediators was blocked by pre-treatment with BAY11-7082, U0126, and SB203580, which are inhibitors of nuclear factor (NF)-κB, ERK1/2, and p38 MAPK, respectively. Enhanced expression of these inflammatory mediators is associated with elevated activation of ERK1/2 in stimulated MPO(-/-) neutrophils. In vivo, MPO(-/-) mice had significantly higher numbers of alveolar neutrophils and increased production of MIP-1α, MIP-1ß, IL-1α, IL-1ß, and TNF-α relative to the responses seen in wild-type mice within 24 h of zymosan administration. CONCLUSION: MPO deficiency upregulates the expression of several proinflammatory cytokines and chemokines in mouse neutrophils.

[A Case of Liver Contusion during Spinal Operation for Idiopathic Scoliosis].

A 20-year-old man diagnosed as idiopathic scoliosis with Cobb angle 146 degrees was scheduled for two-stage operations. Anterior dissection of the thoracic vertebra in the left lateral decubitus position, and the placement of pedicle screws in the prone position were performed as the first-stage operation. During surgery, the patient developed liver contusion with ascites, probably due to hepatic compression placed between vertebrae and operating table in the prone position. In the second operation for posterior spinal fusion, the occurrence of liver contusion was prevented by performing abdominal ultrasonography before and after surgery, and monitoring AST/ALT during anesthesia as the indicators of liver contusion. Intraoperative management for organ protection is required during anesthesia in patients with idiopathic scoliosis associated with thoracic deformity.

Resolution of Inflammation by Resolvin D1 Is Essential for Peroxisome Proliferator-activated Receptor-γ-mediated Analgesia during Postincisional Pain Development in Type 2 Diabetes.

BACKGROUND: The wound healing process following acute inflammation after surgery is impaired in diabetes. Altered macrophage functions are linked to delayed tissue repair and pain development in diabetes. Although peroxisome proliferator-activated receptor (PPAR)-γ agonists are used to treat diabetes, their postoperative analgesic effects in diabetes have not been evaluated. METHODS: The PPARγ agonist rosiglitazone (rosi) was injected at the incision site of diabetic (db/db) mice with resolvin (Rv) D1, a lipid mediator involved in resolution of inflammation. Pain-related behavior, neutrophil infiltration, phagocytosis, and macrophage polarity were assessed for 7 days postoperatively. RESULTS: Rosiglitazone and RvD1 alleviated mechanical hyperalgesia in db/db (db) mice, whereas rosiglitazone alone did not alter mechanical thresholds on days 4 (db rosi + RvD1 vs. db rosi: 0.506 ± 0.106 vs. 0.068 ± 0.12) and 7 (0.529 ± 0.184 vs. 0.153 ± 0.183) after incision (n = 10 per group). In control m/m mice, the rosiglitazone-induced analgesic effects were reversed by knockdown with arachidonate 5-lipoxygenase small interfering RNA, but these were restored by addition of RvD1. In db/db mice treated with rosiglitazone and RvD1, local infiltration of neutrophils was markedly reduced, with an associated decrease in total TdT-mediated dUTP nick-end labeling cells. Acceleration of rosiglitazone-induced phenotype conversion of infiltrated macrophages from M1 to M2 was impaired in db/db mice, but it was effectively restored by RvD1 in db/db wounds. CONCLUSIONS: In diabetes, exogenous administration of RvD1 is essential for PPARγ-mediated analgesia during development of postincisional pain. Resolution of inflammation accelerated by RvD1 might promote PPARγ-mediated macrophage polarization to the M2 phenotype.

Quantitative structure-cytotoxicity relationship of phenylpropanoid amides.

BACKGROUND: A total of 12 phenylpropanoid amides were subjected to quantitative structure-activity relationship (QSAR) analysis, based on their cytotoxicity, tumor selectivity and anti-HIV activity, in order to investigate on their biological activities. MATERIALS AND METHODS: Cytotoxicity against four human oral squamous cell carcinoma (OSCC) cell lines and three human oral normal cells was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. Tumor selectivity was evaluated by the ratio of the mean CC50 (50% cytotoxic concentration) against normal oral cells to that against OSCC cell lines. Anti-HIV activity was evaluated by the ratio of CC50 to EC50 (50% cytoprotective concentration from HIV infection). Physicochemical, structural, and quantum-chemical parameters were calculated based on the conformations optimized by the LowModeMD method followed by density functional theory (DFT) method. RESULTS: Twelve phenylpropanoid amides showed moderate cytotoxicity against both normal and OSCC cell lines. N-Caffeoyl derivatives coupled with vanillylamine and tyramine exhibited relatively higher tumor selectivity. Cytotoxicity against normal cells was correlated with descriptors related to electrostatic interaction such as polar surface area and chemical hardness, whereas cytotoxicity against tumor cells correlated with free energy, surface area and ellipticity. The tumor-selective cytotoxicity correlated with molecular size (surface area) and electrostatic interaction (the maximum electrostatic potential). CONCLUSION: The molecular size, shape and ability for electrostatic interaction are useful parameters for estimating the tumor selectivity of phenylpropanoid amides.

Peripheral administration of morphine attenuates postincisional pain by regulating macrophage polarization through COX-2-dependent pathway.

BACKGROUND: Macrophage infiltration to inflammatory sites promotes wound repair and may be involved in pain hypersensitivity after surgical incision. We recently reported that the development of hyperalgesia during chronic inflammation is regulated by macrophage polarity, often referred to as proinflammatory (M1) or anti-inflammatory (M2) macrophages. Although opioids such as morphine are known to alter the inflammatory milieu of incisional wounds through interactions with immunocytes, the macrophage-mediated effects of morphine on the development of postincisional pain have not been well investigated. In this study, we examined how morphine alters pain hypersensitivity through phenotypic shifts in local macrophages during the course of incision-induced inflammation. RESULTS: Local administration of morphine in the early phase, but not in the late phase alleviated mechanical hyperalgesia, and this effect was reversed by clodronate-induced peripheral depletion of local macrophages. At the morphine-injected incisional sites, the number of pro-inflammatory F4/80+iNOS+M1 macrophages was decreased during the course of pain development whereas increased infiltration of wound healing F4/80+CD206+M2 macrophages was observed during the early phase. Morphine increased the gene expression of endogenous opioid, proenkephalin, and decreased the pronociceptive cytokine, interleukin-1ß. Heme oxygenase (HO)-1 promotes the differentiation of macrophages to the M2 phenotype. An inhibitor of HO-1, tin protoporphyrin reversed morphine-induced analgesic effects and the changes in macrophage phenotype. However, local expression levels of HO-1 were not altered by morphine. Conversely, cyclooxygenase (COX)-2, primarily produced from peripheral macrophages in acute inflammation states, was up-regulated in the early phase at morphine-injected sites. In addition, the analgesic effects and a phenotype switching of infiltrated macrophages by morphine was reversed by local administration of a COX inhibitor, indomethacin. CONCLUSIONS: Local administration of morphine alleviated the development of postincisional pain, possibly by altering macrophage polarity at the incisional sites. A morphine-induced shift in macrophage phenotype may be mediated by a COX-2-dependent mechanism. Therefore, µ-opioid receptor signaling in macrophages may be a potential therapeutic target during the early phase of postincisional pain development.