Preoperative prediction for regaining ambulatory ability in paretic non-ambulatory patients with metastatic spinal cord compression.

STUDY DESIGN: Retrospective multicenter study. OBJECTIVES: To analyze the predictive factors for postoperative ambulatory recovery in paretic non-ambulatory patients with metastatic spinal cord compression (MSCC). SETTING: Japan. METHODS: Eighty-two consecutive patients (74.4% men; mean age, 66.2 years) who could not walk before surgery due to cervical or thoracic MSCC and underwent posterior decompressive surgery between 2003 and 2014 were included. Patients were divided into two groups according to ambulatory status at 6 weeks after surgery: recovery (group R) and non-recovery (group NR). To evaluate the speed of progression of motor deficits, we assessed the period from onset of neurological symptoms to gait inability (T1). RESULTS: Fifty patients (61.0%) regained the ability to walk (group R). The period of T1 demonstrated a positive correlation with probability of ambulatory recovery (P=0.00; Kendall's tau-b=0.38), and a receiver operating characteristic curve analysis showed that the cutoff value of T1 was 5 days (area under the curve=0.72; P=0.001). In multivariate analysis, <6 days of T1 was one of the independent risk factors for failing to regain ambulatory ability (odds ratio, 8.74; P=0.00). CONCLUSIONS: The speed of progression of motor deficits can independently and powerfully predict the chance of postoperative ambulatory recovery as well as previously identified predictors. Since information about the speed of progression can be obtained easily by interviewing patients or family members, even if the patient is in an urgent state, our results will be helpful in clinical decision-making.

Myoferlin regulates cellular lipid metabolism and promotes metastases in triple-negative breast cancer.

Myoferlin is a multiple C2-domain-containing protein that regulates membrane repair, tyrosine kinase receptor function and endocytosis in myoblasts and endothelial cells. Recently it has been reported as overexpressed in several cancers and shown to contribute to proliferation, migration and invasion of cancer cells. We have previously demonstrated that myoferlin regulates epidermal growth factor receptor activity in breast cancer. In the current study, we report a consistent overexpression of myoferlin in triple-negative breast cancer cells (TNBC) over cells originating from other breast cancer subtypes. Using a combination of proteomics, metabolomics and electron microscopy, we demonstrate that myoferlin depletion results in marked alteration of endosomal system and metabolism. Mechanistically, myoferlin depletion caused impaired vesicle traffic that led to a misbalance of saturated/unsaturated fatty acids. This provoked mitochondrial dysfunction in TNBC cells. As a consequence of the major metabolic stress, TNBC cells rapidly triggered AMP activated protein kinase-mediated metabolic reprogramming to glycolysis. This reduced their ability to balance between oxidative phosphorylation and glycolysis, rendering TNBC cells metabolically inflexible, and more sensitive to metabolic drug targeting in vitro. In line with this, our in vivo findings demonstrated a significantly reduced capacity of myoferlin-deficient TNBC cells to metastasise to lungs. The significance of this observation was further supported by clinical data, showing that TNBC patients whose tumors overexpress myoferlin have worst distant metastasis-free and overall survivals. This novel insight into myoferlin function establishes an important link between vesicle traffic, cancer metabolism and progression, offering new diagnostic and therapeutic concepts to develop treatments for TNBC patients.

Gas viscosity measurement with diamagnetic-levitation viscometer based on electromagnetically spinning system.

Utilizing a graphite-disk probe attached with a thin aluminum disk, we have developed a friction-free viscosity measurement system. The probe is levitated above a NdFeB magnet because of diamagnetic effect and rotated by an electromagnetically induced torque. The probe is absolutely free form mechanical friction, and therefore, the accurate measurements of the viscosity of gases can be achieved. To demonstrate the accuracy and sensitivity of our method, we measured the viscosity of 8 kinds of gases and its temperature change from 278 K to 318 K, and we confirmed a good agreement between the obtained values and literature values. This paper demonstrates that our method has the ability to measure the fluid viscosity in the order of µPa ⋅ s.

Relationship between the Peripheral Lymphocyte Response to Mycophenolic Acid in vitro and the Level of ATP in Peripheral CD4+ Lymphocytes before and after Renal Transplantation.

OBJECTIVE: The lymphocyte immunosuppressant sensitivity test has been used to predict the pharmacodynamics of immunosuppressive drugs for the purpose of preventing acute rejection and infection after renal transplantation. On the other hand, measuring the ATP levels in peripheral CD4+ lymphocytes is also able to monitor the risks of rejection and infection in transplant recipients. In the present study, we examined the relationship between the mycophenolic acid pharmacodynamics and the ATP levels in peripheral lymphocytes before and after renal transplantation. METHODS: We examined both the pharmacological efficacy of mycophenolic acid and the lymphocyte ATP levels before and 2, 4 and 6 weeks after the operation in 20 renal transplant recipients. The drug's pharmacological efficacy was evaluated by the 50% inhibitory concentration of the drug against the in vitro proliferation of peripheral blood lymphocytes activated by T cell mitogen. The ATP levels in peripheral CD4+ lymphocytes were measured by the Immuknow assay kit. The relationships between the mycophenolic acid pharmacodynamics and ATP levels in peripheral lymphocytes were examined in these recipients. RESULTS: The immunosuppressive effects of mycophenolic acid against mitogen-activated lymphocyte proliferation were significantly and positively correlated with the lymphocyte ATP levels, but only at 6 weeks after transplantation. The relationship was not significant before or at 2 or 4 weeks after the operation. CONCLUSION: Our present data raised the possibility that evaluating the pharmacological efficacy of mycophenolic acid pre-transplantation and monitoring the ATP level 6 weeks after transplantation can predict the risk of rejection and/or infection in renal transplant recipients.

Value of pre- and postoperative meticillin-resistant Staphylococcus aureus screening in patients undergoing gastroenterological surgery.

BACKGROUND: Data supporting active surveillance of meticillin-resistant Staphylococcus aureus (MRSA) for the prevention of postoperative infection remain controversial. AIM: To investigate the efficacy of MRSA screening in patients undergoing gastroenterological surgery. METHOD: Nasal carriage of MRSA was screened using a polymerase chain reaction (PCR) assay on two gastroenterological surgery wards (A and B). Occurrence of postoperative MRSA infection was analysed according to nasal MRSA carriage status (pre-operative carriage and postoperative acquisition). FINDINGS: The incidence of pre-operative MRSA carriage was 9.7% on Ward A and 4.3% on Ward B (P = 0.009). Postoperative nasal MRSA acquisition was confirmed in 16.2% and 6.0% of patients, respectively (P < 0.001). There was no significant difference in the incidence of MRSA surgical site infections (SSIs) between patients with and without pre-operative nasal colonization on either ward. On Ward A, where MRSA nasal acquisition was more common, the MRSA infection rate in patients with postoperative nasal acquisition was 26.8%, which was significantly higher than the rates in patients with pre-operative MRSA colonization and patients without colonization during hospitalization. Postoperative nasal MRSA acquisition was an independent factor associated with MRSA infection on both wards [Ward A: odds ratio (OR) 7.192, 95% confidence interval (CI) 2.981-17.352; Ward B: OR 5.761, 95% CI 1.429-23.220]. CONCLUSION: MRSA SSIs were prevented by a screening-based strategy in pre-operative MRSA carriers. Postoperative nasal acquisition was a significant factor affecting MRSA infection, and the effect of screening varied according to the incidence of postoperative MRSA acquisition on the ward.

Rewarming preservation by organ perfusion system for donation after cardiac death liver grafts in pigs.

BACKGROUND: Use of grafts from donors after cardiac death (DCD) would greatly contribute to the expansion of the donor organ pool. However, this requires the development of novel preservation methods to recover the organ from changes due to warm ischemia time (WIT). METHODS: Porcine livers were perfused with a newly developed machine perfusion (MP) system. The livers were perfused with modified University of Wisconsin solution (UW) - gluconate. All grafts were procured after acute hemorrhagic shock with the ventilator off. For group 1 (n = 6), grafts were procured after WIT of 60 minutes and preserved by hypothermic MP (HMP) for 3 hours. For group 2 (n = 5), grafts were preserved with 2 hours of simple cold storage (SCS) and HMP for 2 hours. For group 3 (n = 6), grafts were preserved with 2 hours of SCS and rewarming up to 25°C by MP for 2 hours (RMP). The preserved liver grafts were transplanted orthotopically. RESULTS: The alanine aminotransferase level in perfusate in RMP during perfusion preservation was maintained at less than that of HMP. The levels of aspartate aminotransferase and lactate dehydrogenase in the 2 hours after reperfusion were significantly lower in group 3. Histologically, the necrosis of hepatocytes was less severe in group 3. The survival rate in group 3 was 2/4, but 0/4 in the other group. CONCLUSION: RMP is expected to facilitate the recovery of the DCD liver grafts.

Interferon γ and plasminogen activator inhibitor 1 regulate adhesion formation after partial hepatectomy.

BACKGROUND: The pathophysiology of intra-abdominal adhesions has not been studied extensively. The aim of this study was to elucidate the molecular mechanisms underlying adhesion formation in a murine model and in patients undergoing hepatectomy. METHODS: Partial hepatectomy was performed using bipolar forceps in mice. Wild-type mice, antibodies to CD4 and interferon (IFN) γ, IFN-γ, natural killer T (NKT) cells and plasminogen activator inhibitor (PAI) 1 knockout (KO) mice were used. Recombinant hepatocyte growth factor (HGF) was tested for its ability to prevent adhesions. Liver specimens were obtained during surgery from patients undergoing hepatectomy. Adhesion formation was evaluated using a scoring system that ranged from 0 (no adhesions) to 5 (severe adhesions). Levels of IFN-γ and PAI-1 mRNA, and protein concentration of PAI-I were measured, and fluorescence immunostaining was performed. RESULTS: Adhesion formation depended on IFN-γ produced by NKT cells, and NKT KO mice developed few adhesions (mean(s.d.) 1·7(0·3) versus 4·6(0·4) in wild-type mice; P = 0·037). In wild-type mice, the level of PAI-1 mRNA increased after hepatectomy, followed by a decrease in the tissue plasminogen activator (tPA) mRNA level. Adhesion formation was inhibited completely in PAI-1 KO mice (0(0) versus 4·1(0·8) in wild-type mice; P = 0·002). HGF inhibited formation of abdominal adhesions after hepatectomy by reducing IFN-γ and PAI-1 levels, and increasing tPA levels compared with those in mice treated with phosphate-buffered saline (P < 0·001, P = 0·002 and P = 0·035 respectively). In human liver specimens, NKT cells accumulated in the liver after hepatectomy, and PAI-1 expression was increased 5·25-fold (P = 0·030). CONCLUSION: IFN-γ is a key molecule for abdominal adhesion formation after hepatectomy, acting via the reciprocal balance of PAI-1 and tPA. This molecular mechanism may also regulate adhesion formation in patients following hepatectomy. HGF inhibited formation of adhesions by regulating IFN-γ and PAI-1, suggesting that it may be an important target for prevention of adhesions after hepatectomy. SURGICAL RELEVANCE: Postoperative intra-abdominal adhesions can be asymptomatic or cause significant morbidity and mortality. Adhesion formation after hepatectomy has not been studied extensively. In the present study, the molecular mechanisms underlying intra-abdominal adhesions after hepatectomy were investigated in a murine model and in patients. Interferon (IFN) γ produced by natural killer T cells is a key molecule for adhesion formation after hepatectomy in mice, acting via the reciprocal balance between plasminogen activator inhibitor (PAI) 1 and tissue plasminogen activator, the pivotal factors in fibrinolytic activity. This mechanism was also involved in the regulation of adhesions in human tissue samples. Hepatocyte growth factor (HGF) strongly inhibited adhesion formation by regulating IFN-γ and PAI-1. These results indicate that IFN-γ and PAI-1 are possible therapeutic targets, and HGF could prevent postoperative adhesion formation after hepatectomy.

Retention of tocilizumab and anti-tumour necrosis factor drugs in the treatment of rheumatoid arthritis.

OBJECTIVES: The retention of the anti-rheumatic agent tocilizumab (TCZ) has not been well documented in patients with rheumatoid arthritis (RA). We conducted an observational study to compare the retention of TCZ and anti-tumour necrosis factor (TNF) drugs in the treatment of patients with RA. METHOD: We reviewed continuation rates and causes of discontinuation of biological agents (biologics) by assessing medical records of patients with RA who were administered biologics at our institute from September 1999 to April 2012, using the Osaka University Biologics for Rheumatic Diseases (BiRD) registry. RESULTS: A total of 401 patients were included. TCZ, infliximab (IFX), etanercept (ETN), and adalimumab (ADA) were administered to 97, 103, 143, and 58 patients, respectively. There were some differences between the baseline characteristics of the groups. The median duration (range) of TCZ, IFX, ETN, and ADA administration was 2.5 (0.1-12.6), 1.9 (0.0-7.7), 2.9 (0.0-11.3), and 1.3 (0.0-3.4) years, respectively. Continuation rates for TCZ and ETN were significantly higher than those for IFX and ADA. Multivariate analyses showed that discontinuation due to lack or loss of efficacy was significantly less common in the TCZ group than in the other groups. Discontinuation due to overall adverse events was not significantly different between treatment groups. CONCLUSION: TCZ and ETN show better retention than IFX or ADA in the treatment of RA.

Optineurin is potentially associated with TDP-43 and involved in the pathogenesis of inclusion body myositis.

AIMS: Increasing evidences suggest a similarity in the pathophysiological mechanisms of neuronal cell death in amyotrophic lateral sclerosis (ALS) and myofibre degeneration in sporadic inclusion body myositis (sIBM). The aim of this study is to elucidate the involvement of ALS-causing proteins in the pathophysiological mechanisms in sIBM. METHODS: Skeletal muscle biopsy specimens of five patients with sIBM, two with oculopharyngeal muscular dystrophy (OPMD), three with polymyositis (PM), three with dermatomyositis (DM), three with neurogenic muscular atrophy, and three healthy control subjects were examined. We analysed the expression and localization of familial ALS-causing proteins, including transactive response DNA binding protein-43 (TDP-43), fused in sarcoma/translocated in liposarcoma (FUS/TLS), Cu/Zn superoxide dismutase (SOD1) and optineurin (OPTN) by immunohistochemistry. RESULTS: TDP-43, OPTN and, to a lesser extent, FUS/TLS were more frequently accumulated in the cytoplasm in patients with sIBM and OPMD than in patients with PM, DM, neurogenic muscular atrophy, or healthy control subjects. SOD1 was accumulated in a small percentage of myofibres in patients with sIBM and OPMD, and to a very small extent in patients with PM and DM. Confocal microscopy imaging showed that TDP-43 proteins more often colocalized with OPTN than with FUS/TLS, p62 and phosphorylated Tau. CONCLUSIONS: These findings suggest that OPTN in cooperation with TDP-43 might be involved in the pathophysiological mechanisms of skeletal muscular degeneration in myopathy with rimmed vacuoles. Further investigation into these mechanisms is therefore warranted.

Progression of paralysis is the most useful factor for differentiating malignant from benign intramedullary tumors.

STUDY DESIGN: Retrospective study. OBJECTIVES: The purpose of this study was to identify the clinical factors for differentiating malignant from benign intramedullary spinal cord tumors. SETTING: Niigata, Japan. METHODS: We conducted a retrospective review of charts and images. Preoperative paralysis including walking ability, urinary function, magnetic resonance imaging (MRI) findings and pathological diagnosis were evaluated in 33 consecutive cases of intramedullary spinal cord tumor, and the clinical factors that were useful for differentiating malignant from benign tumors were identified. RESULTS: Early progression of paralysis was the most valuable feature for differentiating malignant from benign tumors. Malignant tumors were suspected in only three of ten cases on the basis of MRI findings. CONCLUSION: Simple assessment of walking ability is easy to perform and is useful for predicting the pathological malignancy of intramedullary tumors of the spinal cord.

A basic consideration for porcine liver preservation using a novel continuous machine perfusion device.

INTRODUCTION: The aims of this study were to compare extracellular and intracellular-type University of Wisconsin (UW) solutions for liver grafts and to assess oxygenation in this perfusion system. MATERIALS AND METHODS: The organ preservation system consisted of 3 circulating systems for the portal vein, hepatic artery, and maintenance of the perfusion solution. The portal vein or hepatic artery system had a roller pump, a flow meter, and a pressure sensor. In this study, we perfused livers with UW or extracellular type UW-gluconate at 4°C-6°C for 4 hours. The flow rates at the entrance were 0.5 mL/min/g liver in the portal vein and 0.2 mL/min/liver in the hepatic artery. Orthotopic liver transplantation was performed in pigs: group 1-a, grafts procured after acute hemorrhagic shock were preserved by a solution without O(2); group 1-b, grafts were preserved with O(2); group 2-a, grafts were perfused using intracellular type solution (UW); and group 2-b, grafts were perfused using extracellular-type solution (UW-gluconate). RESULTS: Effluent aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) levels in group 1-b were lower than those in group 1-a. Survival rates in group 2-a and group 2-b were 1/4 and 3/3, respectively. Effluent AST and LDH levels in the perfusate of group 2-b were lower than group 2-a. Histological study revealed necrosis of hepatocytes and sinusoidal congestion in group 2-a. CONCLUSION: A beneficial effect of extracellular-type solution with oxygenation in a novel continuous machine preservation system yielded well-preserved liver graft function.

Associated demographics of persistent exhaled nitric oxide elevation in treated asthmatics.

BACKGROUND: The fraction of exhaled nitric oxide (FENO) is reduced by anti-inflammatory treatment in asthma. However, the FENO level is also regulated by individual demographics and there is considerable variation among clinically stable patients. OBJECTIVE: We hypothesized that some demographics may be responsible for persistent FENO elevation despite inhaled corticosteroids (ICS) therapy in asthma. METHODS: This was a prospective observational study. We initially screened 250 stable asthmatics and determined the FENO cut-off point for identifying poorly controlled asthma defined by one of the following criteria: Asthma control test <20, or forced expiratory volume in one-second % of predicted <80%, or peak expiratory flow variability <80% (Study 1). After 12-weeks, 229 patients who maintained high or low FENO were selected and the independent factors which might contribute to a high FENO were examined (Study 2). RESULTS: A FENO level >39.5 p.p.b. yielded 67% sensitivity and 76% specificity for identifying the patients with poorly controlled asthma. The persistent high FENO group (≥ 40 p.p.b.) was more likely to be ex-smokers, to show evidence of atopy (positive specific IgE, higher serum IgE and blood eosinophils), and to have allergic comorbidities. Especially, past smoking history, blood eosinophils, and chronic rhinosinusitis were identified to be independent predictors of high FENO. Neither the dose of ICS nor other medication use showed any difference between the groups. CONCLUSIONS AND CLINICAL RELEVANCE: These results suggested that past smoking history, blood eosinophilia, and chronic rhinosinusitis are involved in the persistent airway inflammation detected by FENO. Although their relative contributions on FENO values should be further quantified, clarification of the features of the subjects with high FENO might provide clues for adjustment of the treatment approach in asthma.

Native incretins prevent the development of atherosclerotic lesions in apolipoprotein E knockout mice.

AIMS/HYPOTHESIS: Several lines of evidence suggest that incretin-based therapies suppress the development of cardiovascular disease in type 2 diabetes. We investigated the possibility that glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) can prevent the development of atherosclerosis in Apoe (-/-) mice. METHODS: Apoe (-/-) mice (17 weeks old) were administered GLP-1(7-36)amide, GLP-1(9-36)amide, GIP(1-42) or GIP(3-42) for 4 weeks. Aortic atherosclerosis, oxidised LDL-induced foam cell formation and related gene expression in exudate peritoneal macrophages were determined. RESULTS: Administration of GLP-1(7-36)amide or GIP(1-42) significantly suppressed atherosclerotic lesions and macrophage infiltration in the aortic wall, compared with vehicle controls. These effects were cancelled by co-infusion with specific antagonists for GLP-1 and GIP receptors, namely exendin(9-39) or Pro(3)(GIP). The anti-atherosclerotic effects of GLP-1(7-36)amide and GIP(1-42) were associated with significant decreases in foam cell formation and downregulation of CD36 and acyl-coenzyme A:cholesterol acyltransferase-1 (ACAT-1) in macrophages. GLP-1 and GIP receptors were both detected in Apoe (-/-) mouse macrophages. Ex vivo incubation of macrophages with GLP-1(7-36)amide or GIP(1-42) for 48 h significantly suppressed foam cell formation. This effect was wholly abolished in macrophages pretreated with exendin(9-39) or (Pro(3))GIP, or with an adenylate cyclase inhibitor, MDL12,330A, and was mimicked by incubation with an adenylate cyclase activator, forskolin. The inactive forms, GLP-1(9-36)amide and GIP(3-42), had no effects on atherosclerosis and macrophage foam cell formation. CONCLUSIONS/INTERPRETATION: Our study is the first to demonstrate that active forms of GLP-1 and GIP exert anti-atherogenic effects by suppressing macrophage foam cell formation via their own receptors, followed by cAMP activation. Molecular mechanisms underlying these effects are associated with the downregulation of CD36 and ACAT-1 by incretins.

Switching of Na+, K+-ATPase isoforms by salinity and prolactin in the gill of a cichlid fish.

We identified and investigated the changes in expression of two gill Na(+), K(+)-ATPase α-subunit isoforms (α-1a and α-1b) in relationship with salinity acclimation in a cichlid fish, Mozambique tilapia. Transfer of freshwater (FW)-acclimated fish to seawater (SW) resulted in a marked reduction in α-1a expression within 24 h and a significant increase in α-1b expression with maximum levels attained 7 days after the transfer. In contrast, transfer of SW-acclimated fish to FW induced a marked increase in α-1a expression within 2 days, while α-1b expression decreased significantly after 14 days. Hypophysectomy resulted in a virtual shutdown of α-1a mRNA expression in both FW- and SW-acclimated fish, whereas no significant effect was observed in α-1b expression. Replacement therapy by ovine prolactin (oPrl) fully restored α-1a expression in FW-acclimated fish, while cortisol had a modest, but significant, stimulatory effect on α-1a expression. In hypophysectomized fish in SW, replacement therapy with oPrl alone or in combination with cortisol resulted in a marked increase in α-1a mRNA to levels far exceeding those observed in sham-operated fish. Expression of α-1b mRNA was unaffected by hormone treatment either in FW-acclimated fish or in SW-acclimated fish. The mRNA expression of fxyd-11, a regulatory Na(+), K(+)-ATPase subunit, was transiently enhanced during both FW and SW acclimation. In hypophysectomized fish in FW, oPrl and cortisol stimulated fxyd-11 expression in a synergistic manner. The clear Prl dependence of gill α-1a expression may partially explain the importance of this hormone to hyperosmoregulation in this species.

Transcriptional activity and biological effects of mammalian estrogen receptor ligands on three hepatic estrogen receptors in Mozambique tilapia.

Like other fish species, Mozambique tilapia has three forms of estrogen receptor, ERα, ERß1, and ERß2. A primary function of 17ß-estradiol (E(2)) in oviparous species is the hepatic induction of the yolk precursor protein, vitellogenin (Vg). To characterize the roles of ERs in Vg production, transactivation assays and an in vivo study were carried out utilizing agonists for mammalian ERα and ERß, and an antagonist for mammalian ERα, propyl-pyrazole-triol (PPT), diarylpropionitrile (DPN), and methyl-piperidino-pyrazole (MPP), respectively. ERα was more sensitive and responsive to PPT than ERß1 or ERß2 in transactivation assays. All ER isoforms indicated equivalent responsiveness to DPN compared with E(2), although sensitivity to DPN was lower. MPP exhibited antagonistic action on transactivation of all ER isoforms and reduced the E(2) effect on Vg and ERα 48h post-injection. DPN increased ERα and Vg expression and plasma Vg post-injection, whereas PPT was without effect; DPN seems to stimulate Vg production through activation of ERα. The ligand binding domain of all tilapia ER forms shares only 60-65% amino acid identity with human ERα and ERß. This, together with our results, clearly indicates that agonistic or antagonistic characteristics of PPT, DPN and MPP cannot be extrapolated from mammalian to piscine ERs.

Combination joint-preserving surgery for forefoot deformity in patients with rheumatoid arthritis.

Proximal osteotomies for forefoot deformity in patients with rheumatoid arthritis have hitherto not been described. We evaluated combination joint-preserving surgery involving three different proximal osteotomies for such deformities. A total of 30 patients (39 feet) with a mean age of 55.6 years (45 to 67) underwent combined first tarsometatarsal fusion and distal realignment, shortening oblique osteotomies of the bases of the second to fourth metatarsals and a fifth-ray osteotomy. The mean follow-up was 36 months (24 to 68). The mean foot function index scores for pain, disability and activity subscales were 18, 23, and 16 respectively. The mean Japanese Society for Surgery of the Foot score improved significantly from 52.2 (41 to 68) to 89.6 (78 to 97). Post-operatively, 14 patients had forefoot stiffness, but had no disability. Most patients reported highly satisfactory walking ability. Residual deformity and callosities were absent. The mean hallux valgus and intermetatarsal angles decreased from 47.0 degrees (20 degrees to 67 degrees) to 9.0 degrees (2 degrees to 23 degrees) and from 14.1 degrees (9 degrees to 20 degrees) to 4.6 degrees (1 degree to 10 degrees), respectively. Four patients had further surgery including removal of hardware in three and a fifth-ray osteotomy in one. With good peri-operative medical management of rheumatoid arthritis, surgical repositioning of the metatarsophalangeal joint by metatarsal shortening and consequent relaxing of surrounding soft tissues can be successful. In early to intermediate stages of the disease, it can be performed in preference to joint-sacrificing procedures.

Acute salinity challenges in Mozambique and Nile tilapia: differential responses of plasma prolactin, growth hormone and branchial expression of ion transporters.

The responses of Mozambique and Nile tilapia acclimated to fresh water (FW) and brackish water (BW; 17 per thousand) were compared following acute salinity challenges. In both species, plasma osmolality increased to above 450 mOsm by 2h after transfer from FW to seawater (SW); these increases in osmolality were accompanied by unexpected increases in plasma prolactin (PRL). Likewise, PRL receptor gene expression in the gill also increased in both species. In Nile tilapia, hyperosmotic transfers (FW to BW and SW) resulted in increased plasma growth hormone (GH) and in branchial GH receptor gene expression, responses that were absent in Mozambique tilapia. Branchial gene expression of osmotic stress transcription factor 1 (OSTF1) increased in both species following transfer from FW to SW, whereas transfer from BW to SW induced OSTF1 expression only in the Nile tilapia. Branchial expression of Na(+)/Cl(-) cotransporter was higher in FW in both species than in BW. Branchial gene expression of Na(+)/K(+)/2Cl(-) cotransporter (NKCC) increased after transfer from BW to SW in Mozambique tilapia, whereas expression was reduced in the Nile tilapia following the same transfer. The difference in the SW adaptability of these species may be related to a limited capacity of Nile tilapia to up-regulate NKCC gene expression, which is likely to be an essential component in the recruitment of SW-type chloride cells. The differential responses of GH and OSTF1 may also be associated with the disparate SW adaptability of these two tilapiine species.

Comparison of the added value of contrast-enhanced 3D fluid-attenuated inversion recovery and magnetization-prepared rapid acquisition of gradient echo sequences in relation to conventional postcontrast T1-weighted images for the evaluation of leptomeningeal diseases at 3T.

BACKGROUND AND PURPOSE: The usefulness of contrast-enhanced 3D T2-FLAIR MR imaging for the evaluation of leptomeningeal diseases has not been systematically investigated. The purpose of this study was to assess the value added by contrast-enhanced 3D T2-FLAIR and MPRAGE sequences to conventional postcontrast T1-weighted images in the evaluation of leptomeningeal diseases. We also undertook in vitro studies in attempts to understand the consequences of our patient study. MATERIALS AND METHODS: Twelve patients with confirmed leptomeningeal diseases underwent postcontrast T1-weighted, MPRAGE, and 3D T2-FLAIR imaging at 3T. Two radiologists independently assessed the presence of additional information on postcontrast 3D MR images compared with postcontrast T1-weighted images. The effect of different Gd concentrations and flow velocities on the signal intensity on 3D T2-FLAIR images was investigated in vitro. RESULTS: According to both reviewers, 3D T2-FLAIR images yielded significantly more information than did MPRAGE images (P < .05 and P < .01, respectively). In the in vitro study, 3D T2-FLAIR was more highly sensitive to low Gd concentrations and less sensitive to high Gd concentrations than were T1-weighted or MPRAGE sequences. On 3D T2-FLAIR sequences, at a flow velocity exceeding 1.0 cm/s, the signal intensity of blood-mimicking fluids at concentrations of 0 and 0.1 mmol/L was as low as at 1.3 mmol/L. CONCLUSIONS: For the depiction of leptomeningeal diseases, postcontrast 3D T2-FLAIR provides more additional information than postcontrast MPRAGE imaging. The superiority of the 3D T2-FLAIR sequence is associated with its high sensitivity to flow.

Effects of instant coffee consumption on oxidative DNA damage, DNA repair, and redox system in mouse liver.

To examine the effects of instant coffee consumption on cancer risk, we analyzed the oxidative DNA damage levels and the DNA repair and redox systems in the livers of coffee-fed mice. Three-week-old male ICR mice were fed with/without 0.1% (w/v) instant coffee solution. At 2, 4, and 8 mo, the levels of 8-hydroxydeoxyguanosine (8-OH-dG), a major form of oxidative DNA damage, and the expression of mouse 8-OH-dG repair-associated genes and redox system-associated genes, the SOD activity, and the LPO level were analyzed. Simultaneously, half of the mice were fed a low vitamin (LV) diet (autoclaved diet) to disturb the defense system against oxidative stresses. As a result, the 8-OH-dG level was increased in the livers of LV diet (+ water)-fed mice for 8 mo, in comparison to those of the 0 M control mice and normal diet (+ water)-fed mice. However, no significant differences between water drinking and coffee drinking were observed, in terms of the 8-OH-dG level. In addition, the 8-OH-dG repair-associated gene expression, the SOD activity, and the LPO level also showed no significant differences between water drinking and coffee drinking in all mouse groups. On the other hand, among the redox system-associated genes, only the expression of GPx1 was changed. These results suggest that instant coffee consumption has little, if any, effect on the risk of liver cancer due to oxidative stresses.