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['Excessive apoptosis of osteoblasts is the major cause of low bone mass, and bovine lactoferrin (bLF), an iron-binding glycoprotein, might protect osteoblastic cells from apoptosis induced by serum withdrawal. The aim of this study was to elucidate the mechanisms underlying the anti-apoptotic action of bLF in rat osteoblasts in vitro.', 'Primary rat osteoblasts were incubated in the presence of varying concentrations of bLF for 24 h. The expression of insulin-like growth factor I (IGF-I) and IGF-I receptor (IGF-IR) was measured uisng RT-PCR and Western blotting. Cell apoptosis was examined with flow cytometry. siRNAs targeting IGF-I was used in this study.', 'Treatment of bLF (0.1-1000 μg/mL) dose-dependently increased the expression of IGF-I and IGF-IR in the osteoblasts. Treatment with bLF (10, 100 μg/mL) markedly inhibited the osteoblast apoptosis (with the rate of total apoptosis of 70% at 10 μg/mL), but the high concentration of bLF (1000 μg/mL) significantly promoted the osteoblast apoptosis. Knockdown of the IGF-I gene in osteoblasts with siRNA markedly increased the osteoblast apoptosis.'] |
['This study evaluated whether sildenafil citrate, an oral treatment for erectile dysfunction and a selective inhibitor of phosphodiesterase type 5 (PDE5) with modest vasodilating properties, affects cardiac contractility in vitro.', 'Slices of freshly obtained human (n = 2) or dog (n = 3) atrial appendage were suspended in organ baths containing Krebs-Ringer bicarbonate buffer (pH 7.4, 37 degrees C) bubbled continuously with 95% O2 and 5% CO2, and isometric tension was recorded using a Gould physiograph. Contractions were elicited by 1-Hz electric pacing. After 15 min of equilibration, 1 microM sildenafil was added to the bath, followed 15 min later (human and dog) by 5 microM epinephrine, an inotropic agent, and 10 min later (dog) by 88 microM 3-isobutyl-1-methylxanthine (IBMX), a nonselective PDE inhibitor. In a separate experiment, cyclic guanosine monophosphate levels and PDE, protein kinase G, and protein kinase A activities were determined.', 'Addition of 1 microM sildenafil to isolated dog or human atrial tissue had no significant effect on force of cardiac contraction, whereas epinephrine produced a robust increase in contractile force in the same muscle strip. The addition of IBMX produced a marked stimulation of contractile force in dog atrial tissue. Very low amounts of PDE5 were found in extracts of human heart, consistent with its known primary location in the smooth muscle of systemic vasculature.'] |
['Myeloid cells have been suggested to participate in angiogenesis and regulation of vascular function. Shb-deficient mice display both vascular and myeloid cell abnormalities with possible consequences for recovery after hindlimb ischaemia. This study was conducted in order to assess the contribution of Shb deficiency in myeloid cells to impaired vascular function in ischaemia.', 'Wild type and Shb-deficient mice were subjected to peritoneal vascular endothelial growth factor A (VEGFA) followed by intraperitoneal lavage, after which blood and peritoneal cells were stained for myeloid markers. VEGFA-induced leucocyte recruitment to cremaster muscle was investigated using intravital microscopy of both mouse strains. Blood flow after femoral artery ligation was determined on chimeric mice after bone marrow transplantation.', 'No differences in neutrophil numbers or cell surface phenotypes were detected. Moreover, neutrophil extravasation in VEGFA-activated cremaster muscle was unaffected by Shb deficiency. However, blood and peritoneal CXCR4+ monocytes/macrophages were reduced in response to intraperitoneal VEGFA but not lipopolysaccharide (LPS) in the absence of Shb. Furthermore, the macrophage population in ischaemic muscle was unaffected by Shb deficiency after 2 days but reduced 7 days after injury. The bone marrow transplantation experiments revealed that mice with wild type vasculature showed better blood flow than those with Shb-deficient vasculature irrespective of leucocyte genotype.'] |
['To test the hypothesis that ultrasound-guided foam sclerotherapy (UGFS) is a safe and durable treatment for superficial venous reflux (SVR) associated with CEAP clinical grade 2-6 disease.', 'This was an interrogation of a prospectively gathered computerized database.', 'Between March 23, 2004 and December 31, 2009, 977 patients (1252 legs) underwent UGFS for unilateral (702 legs) or bilateral (550 legs) SVR in association with CEAP clinical grade 2-3 (n = 868), 4 (n = 232), or 5/6 (n = 152) disease. The following reflux in 1417 venous segments was treated: primary great saphenous vein (GSV) (n = 745); recurrent GSV (n = 286), primary small saphenous vein (SSV) (n = 189), recurrent SSV (n = 50); primary anterior accessory saphenous vein (AASV) (n = 93); recurrent AASV (n = 46); vein of the popliteal fossa (VOPF) (n = 5), and Giacomini vein (GV) (n = 3). Three hundred forty-eight legs (27.8%) had undergone previous surgery. Three patients suffered post-UGFS deep vein thrombosis (DVT) and one a pulmonary embolus (PE), all within the first month (0.4% venous thrombo-embolic complication rate). Five patients (0.5%) had transient visual disturbance at the time of, or shortly after, treatment. No other neurologic or serious complications were reported. During a mean (range) follow-up of 28 (<1 to 68) months, 161 (12.9%) legs underwent a further session of UGFS for truncal VV at a mean (range) of 17 (<1 to 63) months following the first treatment. In 52 legs, retreatment was due to the development of new SVR and in 109 legs was for true recurrence (8.7% complete or partial recanalization rate leading to treatment). There was no significant difference in retreatment rates between UGFS for GSV and SSV reflux or between UGFS for primary or recurrent disease.'] |
['We investigated whether BB-882, a novel potent PAF antagonist, could influence systemic and pulmonary hemodynamics and oxygen extraction capabilities during an acute reduction in blood flow induced by cardiac tamponade after endotoxin challenge.', 'Twenty-one anesthetized, ventilated, and endotoxin-shocked (2 mg/kg i.v. Escherichia coli endotoxin) dogs were randomly divided in three groups. One group (N = 7) served as control. A second group (N = 7) received BB-882 as a single bolus dose of 5 mg/kg, 30 minutes before endotoxin administration. A third group (N = 7) received BB-882 as a continuous infusion of 5 mg/kg x h, started 30 minutes after endotoxin. Hemodynamic and gazometric measurements were obtained in all dogs 30 minutes after endotoxin injection and repeated 30 minutes after cardiac filling pressures were restored to baseline by generous saline infusion. Saline infusion rate was then set at 20 mL/kg x h and tamponade was induced by repeated bolus injections of warm saline into the pericardial sac.', 'Compared with controls, pretreatment with BB-882 attenuated the early endotoxin-induced decrease in arterial pressure (70 +/- 17 v 51 +/- 14 mm Hg, P < .05), cardiac index (118 +/- 29 v 91 +/- 15 mL/ kg x min, P < .05), stroke index (1.0 +/- 0.2 v 0.7 +/- 0.3 mL/kg, P < .05), and left ventricular stroke work index (0.9 +/- 0.3 v 0.4 +/- 0.2 g x m/kg, P < .05), but these effects were not sustained after fluid resuscitation. In contrast, BB-882 post-treatment maintained arterial pressure and improved cardiac performance at lower filling pressures in the later phase of endotoxic shock. BB-882 did not influence pulmonary hemodynamics. Treatment with BB-882 did not influence oxygen extraction at critical oxygen delivery (51.5 +/- 9.9% and 52.8 +/- 13.9% v 46.6 +/- 9.0%, respectively BB-882 pretreatment and post-treatment v control).'] |
['Arthroscopic microfracture (AM) of osteochondral lesions of the talus is used to induce intrinsic refilling of the defect and reduce pain. The aim of this retrospective study was to investigate the clinical state after AM and the MRI outcome.', 'A total of 22 patients [10 women, 12 men, 31\xa0years old (mean, 13-68 range)] treated for osteochondral lesions of the talus by AM were examined 2\xa0years (median) postoperatively and pre- and postoperative MRI results compared. Swelling/effusion, articular constriction, joint pain, and range of motion restriction were documented. Clinical state was evaluated using the AOFAS hindfoot score. MRI was used to assess the size of the defect, presence of bone marrow edema, cysts and effusion, thickness of repair tissue, and integrity of the cartilage.', 'In all but six cases, the defect was located at the medial shoulder of the talus. The postoperative AOFAS score at follow-up was 87.5\xa0points (median 36-100\xa0points range). Seven patients were free of pain, 11 had "mild, occasional" pain, 1 "moderate daily", and 3 "severe, almost always present" pain (AOFAS). The defect volume was significantly reduced from 377\xa0mm(3) preoperatively (median, interquartile distance: 417\xa0mm(3)) to 249\xa0mm(3) postoperatively (median, IQD: 336\xa0mm(3), p\xa0=\xa00.019, Wilcoxon). In 7 cases, the defect was completely filled, in 11 partially and in 4 only slightly.'] |
['Patients with rheumatoid arthritis have low plasma vitamin B(6) levels and elevated plasma homocysteine responses to a methionine load. We examined whether these abnormalities are associated with clinical and biochemical indicators of disease status.', "We performed a cross-sectional study in 37 patients who met the American College of Rheumatology criteria for rheumatoid arthritis. Vitamin B(6) status was assessed by the plasma pyridoxal 5'-phosphate level and with the homocysteine response to a methionine load test. Clinical disease activity was assessed by joint counts, the Health Assessment Questionnaire disability score, and biochemical markers of the acute phase response.", "Plasma pyridoxal 5'-phosphate levels were inversely correlated with the erythrocyte sedimentation rate (r = -0.37, P = 0.02), C-reactive protein level (r = -0.52, P = 0.002), disability score (r = -0.37, P = 0.02), morning stiffness (r = -0.38, P = 0.02), and degree of pain (r = -0.33, P = 0.04). The increase in homocysteine levels after a methionine load correlated with the erythrocyte sedimentation rate (r = 0.39, P = 0.02), C-reactive protein level (r = 0.37, P = 0.03), disability score (r = 0.37, P = 0.04), degree of pain (r = 0.38, P = 0.02) and fatigue (r = 0.42, P = 0.01), number of painful joints (r = 0.43, P = 0.007), and number of swollen joints (r = 0.32, P = 0.05)."] |
['Ischemic stroke may result from transient or permanent reductions of regional cerebral blood flow. Polymorphonuclear neutrophils have been described as the earliest inflammatory cells to arrive in ischemic tissue. CXCR1/2 receptors are involved in the recruitment of these cells. However, the contribution of these chemokine receptors during transient brain ischemia in mice remains poorly understood. In this work, we investigated the effects of reparixin, an allosteric antagonist of CXCR1/2 receptors, in a model of middle cerebral artery occlusion and reperfusion in mice.', 'C57BL/6J male mice treated with reparixin or vehicle were subjected to a middle cerebral artery occlusion procedure 1 h after the treatment. Ninety minutes after ischemia induction, the monofilament that prevented blood flow was removed. Twenty-four hours after the reperfusion procedure, behavioral changes, including motor signs, were analyzed with the SmithKline/Harwell/lmperial College/Royal Hospital/Phenotype Assessment (SHIRPA) battery. The animals were sacrificed, and brain tissue was removed for histological and biochemical analyses. Histological sections were stained with hematoxylin and eosin, neutrophil infiltration was estimated by myeloperoxidase activity and the inflammatory cytokine IL-iβ was measured by ELISA.', 'Pre-treatment with reparixin reduced the motor deficits observed in this model of ischemia and reperfusion. Myeloperoxidase activity and IL-iβ were reduced in the reparixin-treated group. Histological analysis revealed that ischemic injury was also attenuated by reparixin pre-treatment.'] |
['Echinostoma caproni (Trematoda: Echinostomatidae) is an intestinal trematode, which has been widely employed to investigate the factors determining the rejection of intestinal helminths. Protein production patterns of intestinal epithelial cells are related to the infection-induced changes that determine the course of E. caproni infections. Herein, we compare the protein production profiles in the ileum of four experimental groups of mice: control; infected; dewormed and reinfected. Worm burdens were significantly lower in secondary infections, confirming the generation of partial resistance to homologous secondary infections in mice. However, quantitative comparison by 2D-DIGE showed that the protein production profile is similar in control and dewormed mice, and after primary and secondary E. caproni infections. These results showed that, unexpectedly, protein production changes in E. caproni infections are not responsible of resistance development. Fifty-one protein spots were differentially produced between control/treated and infected/reinfected mice and 37 of them were identified by mass spectrometry. The analysis of differentially abundant proteins indicate that cell metabolism and the regulation of proliferation and cell death are the most affected processes after primary and secondary E. caproni infections. These results provide new insights into the proteins involved in the regulation of tissue homeostasis after intestinal infection.'] |
['To report on bevacizumab treatment for radiation retinopathy affecting the macula.', 'Twenty-one patients with radiation retinopathy (edema, hemorrhages, capillary dropout, and neovascularization) and a subjective or objective loss of vision were treated. Treatment involved intravitreal injection of bevacizumab (1.25 mg in 0.05 mL) every 6-12 weeks. Treatment was discontinued at patient request or if there was no measurable response to therapy. Main outcome measures included best corrected visual acuity, ophthalmic examination, retinal photography, and angiography.', 'Bevacizumab treatment was followed by reductions in retinal hemorrhage, exudation, and edema. Visual acuities were stable or improved in 86% (n=18). Three patients discontinued therapy. Each was legally blind before treatment (n=1), experienced little to no subjective improvement (n=2), or was poorly compliant (n=2). Three patients (14%) regained 2 or more lines of visual acuity. No ocular or systemic bevacizumab-related side effects were observed.'] |
['Spontaneous electrical activity, termed slow waves, drives rhythmic, propulsive contractions in the smooth muscle of the oviduct (myosalpinx). Myosalpinx contractions cause egg transport through the oviduct. Agents that disrupt slow wave pacemaker activity will therefore disrupt myosalpinx contractions and egg transport. Caffeine is commonly used as a ryanodine receptor agonist and has been previously associated with delayed conception. Here we assessed the effects of caffeine on pacemaker activity in the murine myosalpinx.', 'The effects of caffeine on electrical pacemaker activity were studied using intracellular microelectrode and isometric force measurements on intact oviduct muscle preparations. Responses to caffeine were compared with responses caused by 3-isobutyl-1-methylxanthine (IBMX) and forskolin.', 'Caffeine caused hyperpolarization of membrane potential and inhibited slow wave generation and myosalpinx contractions. The effects of caffeine could be mimicked by the K(ATP) channel agonist pinacidil and antagonized by the K(ATP) channel antagonist glibenclamide. Caffeine is known to inhibit cyclic nucleotide phosphodiesterases (PDEs), leading to an increase in cytosolic cAMP and stimulation of downstream cAMP-dependent mechanisms. The effects of caffeine were mimicked by the PDE inhibitor, IBMX, and the adenylyl cyclase activator forskolin. These effects were also reversed by glibenclamide.'] |
['A pacemaker system is required for peristalsis generation. The interstitial cells of Cajal (ICC) are considered the intestinal pacemaker, and are identified by expression of the c-kit gene--encoded protein. Gastroschisis is characterized by a severe gastrointestinal dysmotility in newborns. In spite of this clinical picture, few studies have focused on smooth muscle cells (SMC) morphology and none on ICC. Therefore, their morphology has been studied in fetuses at term in the rat model of gastroschisis.', "At 18.5 day's gestation (E18.5), 10 rat fetuses were killed, 10 underwent surgical creation of gastroschisis, and 10 underwent manipulation only. The small intestine of the latter 2 groups was harvested at E21.5. Specimens were processed for H&E, c-kit and actin (alpha smooth muscle antibody [alpha-SMA]) immunohistochemistry, and transmission electron microscopy (TEM).", "In the controls, SMC were c-kit+ and alpha-SMA+, with labeling intensity increasing by age. At E21.5, some cells around the Auerbach's plexus were more intensely c-kit+, and differentiating ICC were seen under TEM at this level. Gastroschisis fetuses had no c-kit+ cells referable to ICC. In the more damaged loops, SMC were very faintly c-kit+ and alpha-SMA+. Under TEM, there were few differentiated SMC and no presumptive ICC. In the less-damaged loops, SMC were faintly c-kit+ and alpha-SMA+ and had ultrastructural features intermediate between those of E18.5 and E21.5 controls; ICC were very immature."] |
['The aim of this study was to determine whether ascorbic acid (AsA) deficiency-induced endotoxin influx into portal blood from the gastrointestinal tract contributes to the inflammatory changes in the liver.', 'The mechanisms by which AsA deficiency provokes inflammatory changes in the liver were investigated in Osteogenic Disorder Shionogi (ODS) rats (which are unable to synthesize AsA). Male ODS rats (6-wk-old) were fed a diet containing sufficient (300\xa0mg/kg) AsA (control group) or a diet without AsA (AsA-deficient group) for 14 or 18\xa0d.', 'On day 14, the hepatic mRNA levels of acute-phase proteins and inflammation-related genes were significantly higher in the AsA-deficient group than the control group, and these elevations by AsA deficiency were exacerbated on day 18. The serum concentrations of interleukin (IL)-1β and IL-6, which induce acute-phase proteins in the liver, were also significantly elevated on day 14 in the AsA-deficient group compared with the respective values in the control group. IL-1β mRNA levels in the liver, spleen, and lung were increased by AsA deficiency. Moreover, on both days 14 and 18, the portal blood endotoxin concentration was significantly higher in the AsA-deficient group than in the control group, and a significant correlation between serum IL-1β concentrations and portal endotoxin concentrations was found in AsA-deficient rats. In the histologic analysis of the ileum tissues, the number of goblet cells per villi was increased by AsA deficiency.'] |
['We applied a low-intensity pulsed transcranial ultrasound stimulation (pTUS) to the ischemic cortex after a distal middle cerebral artery occlusion (dMCAO) to study whether pTUS is capable of protecting brain from ischemic injury.', 'Rats were randomly assigned to Sham (n = 6), Control (n = 16), and pTUS (n = 16) groups. The pTUS-treated rats were subjected to 60-min ultrasonic stimulation immediately after the ischemia. After 48 h, the sensorimotor-related behavioral outcomes were assessed by a neurological severity score (NSS), and the permanent brain injury was assessed by the histologic analysis of TTC staining of brain slices.', 'pTUS group showed significantly lower NSS (n = 10, 5.5 ± 2.5) than the Control group ( n = 10, 10.5 ±1.4) (p < 0.01). Concordantly, the ischemic lesion was significantly reduced after receiving pTUS immediately after dMCAO. The cortical infarct volume in the control group was more than threefold of the pTUS group (43.39% ± 2.33%, n = 16 versus 13.78% ± 8.18%, n = 16, p < 0.01). Immunohistochemical staining indicated reduction of neutrophils in the affected area, and laser speckle imaging showed significant increase of a cerebral blood flow after pTUS, which consistently supported the neuroprotection of pTUS in ischemic brain injury.'] |
['We examined whether B-type natriuretic peptide (BNP) levels predict outcome in heart failure patients with implantable cardioverter defibrillators (ICD) using a combined endpoint of malignant tachyarrhythmias, death or heart transplantation.', 'BNP levels were measured in 123 ICD patients with chronic heart failure (age: 63+/-12 years, ejection fraction: 29+/-10%). After a median follow-up of 25 months, the combined endpoint was reached in 28 patients (first tachyarrhythmic event, n=16; death, n=11; heart transplantation, n=1). BNP levels were significantly lower in patients with event-free survival compared to patients reaching the combined endpoint of this study (median: 140 vs. 373 pg/ml; p<0.001). Multivariable Cox regression analysis revealed that BNP levels predict adverse outcome (RR 1.002 per pg/ml increment; 95% CI: 1.001-1.003; p<0.001) and use of beta-blockers was associated with favourable outcome (RR 0.319; 95% CI 0.151-0.670; p=0.004). LV ejection fraction (p=0.66) did not significantly predict event-free survival in multivariable analysis.'] |
['The urokinase-type plasminogen activator receptor (uPAR) is an important regulator of ECM proteolysis, cell-ECM interactions and cell signaling. uPAR and heat shock proteins HSP70 and MRJ (DNAJB6) have been implicated in tumor growth and metastasis. We have reported recently that MRJ (DNAJB6, a heat shock protein) can interact with uPAR and enhance cell adhesion. Here, we identified another heat shock protein HSP70 as a novel uPAR-interacting protein.', 'We performed co-immunoprecipitation in human embryonic kidney (HEK) 293 and colon cancer HCT116 cells as well as immunofluorence assays in HEK293 cells stably transfected with uPAR to investigate the association of suPAR with HSP70/MRJ. To understand the biological functions of the triple complex of suPAR/HSP70/MRJ, we determined whether HSP70 and/or MRJ regulated uPAR-mediated cell invasion, migration, adhesion to vitronectin and MAPK pathway in two pair of human tumor cells (uPAR negative HEK293 cells vs HEK293 cells stably transfected with uPAR and HCT116 cells stably transfected with antisense-uPAR vs HCT116 mock cells transfected with vector only) using transwell assay, wound healing assay, quantitative RT-PCR analyzing mmp2 and mmp9 transcription levels, cell adhesion assay and Western blotting assay.', 'HSP70 and MRJ formed a triple complex with uPAR and over-expression of MRJ enhanced the interaction between HSP70 and uPAR, while knockdown of MRJ decreased soluble uPAR in HCT116 cells (P\u2009<\u20090.05) and reduced the formation of the triple complex, suggesting that MRJ may act as an uPAR-specific adaptor protein to link uPAR to HSP70. Further experiments showed that knockdown of HSP70 and/or MRJ by siRNA inhibited uPAR-mediated cell adhesion to vitronectin as well as suppressed cell invasion and migration. Knockdown of HSP70 and/or MRJ inhibited expression of invasion related genes mmp2 and mmp9. Finally, HSP70 and/or MRJ up-regulated phosphorylation levels of ERK1/2 and FAK suggesting MAPK pathway was involved. All the biological function experiments in cell level showed an additive effect when HSP70 and MRJ were regulated simultaneously indicating their collaborated regulation effects on uPAR.'] |
['Toxoplasma gondii, an obligate intracellular parasite, can invade intestinal epithelial cells and elicit a robust Th1 immune response. In this model of intestinal inflammation, CD8(+) intraepithelial lymphocytes (IELs) secrete transforming growth factor (TGF)-beta, which appears necessary for the maintenance of homeostasis in the intestine. However, the mechanism responsible for the IEL migration to the inflamed intestine is still unclear.', 'An in vitro coculture cell system was used to quantify the IEL attraction by an infected intestinal epithelial cell line (m-IC(cl2)). We used CCR5-deficient mice to determine which chemokine receptor-chemokine interaction could be responsible for the recruitment of antigen-specific CD8(+) IELs to the small intestine for the promotion of parasite clearance and host recovery.', 'We observed increased expression of several chemokine receptors (CCR1, CCR2, CCR5, CXCR3) in the infected ileum. In particular, CCR5 expression was markedly increased in antigen-primed CD8(+) IELs. Experiments using recombinant chemokines as well as blocking antibodies showed that macrophage inflammatory protein (MIP)-1alpha and MIP-1beta were critical for their homing. CD8(+) IELs isolated from CCR5-deficient mice (CCR5-/-), despite their high production of TGF-beta and overexpression of activation markers, were impaired in their ability to migrate in vitro to the m-IC(cl2) monolayer or in vivo to the inflamed intestine after adoptive transfer.'] |
['The association between perinatal factors and asthma inception is under rigorous investigation. Nevertheless, evidence of a correlation between asthma, conception via in vitro fertilization (IVF) and delivery through Caesarean section (C-section) is inconclusive.', 'We aimed to assess the relation of asthma incidence with IVF and C-section, after controlling for several potential confounding factors.', "Parent-reported wheeze in the last 12 months (current), wheeze ever, physician-diagnosed asthma, method of conception, and type of delivery were recorded from questionnaires filled in by the parents of 2016 Greek children aged 9-13, (the Healthy Growth Study population). Some perinatal data were recorded from children's medical records and others were reported by parents; anthropometric measurements were also conducted in children.", 'IVF was correlated with physician-diagnosed asthma (OR = 2.25; 95% CI = 1.11-4.56), but not with current/ever wheeze after adjustment for potential confounding factors. After adjustment, C-section was also associated with asthma (OR = 1.39; 95% CI = 1.04-1.87), but not with current/ever wheeze. When the association of both IVF and C-section with asthma was examined in the same multivariate logistic regression model, it was weakened to borderline significance (OR = 2.04; 95% CI = 1-4.15 and OR = 1.34; 95% CI = 1-1.81 respectively).'] |
['The phenotypic expression of X-linked adrenoleukodystrophy (X-ALD) ranges from the rapidly progressive childhood cerebral form to the milder adrenomyeloneuropathy in adults. It is not possible to predict phenotype by mutation analysis or biochemical assays. Multislice proton MRS imaging (MRSI) has previously detected more extensive brain abnormalities in X-ALD than conventional MRI, which has been suggested to predict impending demyelination. However, the significance of these changes is unclear.', 'The purpose of this study was to determine the long-term sensitivity and specificity of MRSI for disease progression in X-ALD.', 'Twenty-five patients with X-ALD were investigated (average age, 15 years; range, 2-43 years) with MRI and proton MRSI at baseline and follow-up MRI over a mean period of 3.5 years. Eight patients had normal MRI findings at baseline and on follow-up (noncerebral group), 11 had abnormal MRI at baseline and no change on follow-up (cerebral nonprogressive group), and 6 had progressive MRI abnormalities (cerebral progressive group). On MRSI, voxels were analyzed in the normal MRI-appearing perilesional white matter, or in the corresponding area in the noncerebral group.', 'The concentration ratio of N-acetylaspartate (NAA) to choline was the most sensitive indicator of disease progression. The average NAA/choline ratio was 5.99 for the noncerebral group, 5.75 for the cerebral nonprogressive group, and 3.74 for the cerebral progressive group (p = 0.002). At a cut-off point of 5.0, the NAA/choline ratio predicted disease progression in all patients with six cerebral progressive disease (sensitivity 100%). The specificity was 83%, the positive predictive value was 66%, and the negative predictive value was 100%.'] |
['Ezrin-radixin-moesin proteins are cross-linkers between the plasma membrane and actin filaments. Radixin, the dominant ezrin-radixin-moesin protein in hepatocytes, has been reported to selectively tether multidrug-resistance-associated protein 2 to the apical canalicular membrane. However, it remains to be determined if this is its primary function.', 'An adenovirus-mediated short interfering RNA (siRNA) was used to down-regulate radixin expression in collagen sandwich-cultured rat hepatocytes and morphologic and functional changes were characterized quantitatively.', 'In control cultures, an extensive bile canalicular network developed with properly localized apical and basolateral transporters that provided for functional excretion of fluorescent cholephiles into the bile canalicular lumina. siRNA-induced suppression of radixin was associated with a marked reduction in the canalicular membrane structure as observed by differential interference contrast microscopy and F-actin staining, in contrast to control cells exposed to adenovirus encoding scrambled siRNA. Indirect immunofluorescence showed that apical transporters (multidrug-resistance-associated protein 2, bile salt export pump, and multidrug-resistance protein 1) dissociated from their normal location at the apical membrane and were found largely associated with Rab11-containing endosomes. Localization of the basolateral membrane transporter, organic anion transporting polypeptide 2 (Oatp2), was not affected. Consistent with this dislocation of apical transporters, the biliary excretion of glutathione-methylfluorescein and cholylglycylamido-fluorescein was decreased significantly in the radixin-deficient cells, but not in the control siRNA cells.'] |
['Myocarditis is an inflammatory disorder of the heart in which T lymphocytes have a central role. No effective treatment is currently at hand for management of the myocarditis. Lymphocyte function requires the active signal transducer Ras. We thus hypothesized that S-farnesylthiosalicylic acid (FTS), a synthetic small molecule that detaches Ras from the inner cell membrane and induces its rapid degradation, will attenuate experimental autoimmune myocarditis (EAM).', 'Two groups of Lewis rats were induced to develop EAM by immunization with porcine cardiac myosin. Group A received 5 mg/kg of FTS, and group B received phosphate-buffered saline (PBS) according to two protocols: FTS or PBS was given 2 days before myosin immunization in protocol 1 and FTS or PBS was given 14 days after myosin immunization in protocol 2. FTS significantly suppressed myocarditis, and this effect was accompanied by a reduction in myosin-specific cellular and humoral immune responses. In the longer regimen, FTS treatment for 6 weeks was associated with preservation of myocardial function made evident by echocardiography. In vitro, FTS significantly attenuated the proliferation of lymphocytes from untreated myocarditic rats to myosin.'] |
['Pathological complete remission (pCR) of estrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer is rarely achieved after neoadjuvant chemotherapy (NAC). In addition, the prognostic value of pCR for this breast cancer subtype is limited. We explored whether response evaluation by magnetic resonance imaging (MRI) is associated with recurrence-free survival after NAC in ER-positive/HER2-negative breast cancer.', 'MRI examinations were performed in 272 women with ER-positive/HER2-negative breast cancer before, during and after NAC. MRI interpretation included lesion morphology at baseline, changes in morphology and size, and contrast uptake kinetics. These MRI features, clinical characteristics and final pathology were correlated with recurrence-free survival.', 'The median follow up time was 41 months. There were 35 women with events, including 19 breast-cancer-related deaths. On multivariable analysis, age younger than 50 years (hazard ratio (HR)\u2009=\u20092.55, 95 % confidence interval (CI) 1.3, 5.02, p\u2009=\u20090.007), radiological complete response after NAC (HR\u2009=\u200914.11, CI 1.81, 1818; p\u2009=\u20090.006) and smaller diameters of washout/plateau enhancement at MRI after NAC (HR\u2009=\u20091.02, CI 1.00, 1.04, p\u2009=\u20090.036) were independently associated with best recurrence-free survival. Pathological response was not significant; HR\u2009=\u20092.12, CI 0.86, 4.64, p\u2009=\u20090.096.'] |
['Buprenorphine is an effective treatment for opioid dependence that can be provided in a primary care setting. Offering this treatment may also facilitate the identification and treatment of other chronic medical conditions.', 'We retrospectively reviewed the medical records of 168 patients who presented to a primary care clinic for treatment of opioid dependence and who received a prescription for sublingual buprenorphine within a month of their initial visit.', 'Of the 168 new patients, 122 (73%) did not report having an established primary care provider at the time of the initial visit. One hundred and twenty-five patients (74%) reported at least one established chronic condition at the initial visit. Of the 215 established diagnoses documented on the initial visit, 146 (68%) were not being actively treated; treatment was initiated for 70 (48%) of these within one year. At least one new chronic medical condition was identified in 47 patients (28%) during the first four months of their care. Treatment was initiated for 39 of the 54 new diagnoses (72%) within the first year.'] |
['Although mitochondrial dysfunction is consistently manifested in patients with Type 2 Diabetes mellitus (T2DM), the association of mitochondrial DNA (mtDNA) sequence variants with T2DM varies among populations. These differences might stem from differing environmental influences among populations. However, other potentially important considerations emanate from the very nature of mitochondrial genetics, namely the notable high degree of partitioning in the distribution of human mtDNA variants among populations, as well as the interaction of mtDNA and nuclear DNA-encoded factors working in concert to govern mitochondrial function. We hypothesized that association of mtDNA genetic variants with T2DM could be revealed while controlling for the effect of additional inherited factors, reflected in family history information.', "To test this hypothesis we set out to investigate whether mtDNA genetic variants will be differentially associated with T2DM depending on the diabetes status of the parents. To this end, association of mtDNA genetic backgrounds (haplogroups) with T2DM was assessed in 1055 Jewish patients with and without T2DM parents ('DP' and 'HP', respectively).", "Haplogroup J1 was found to be 2.4 fold under-represented in the 'HP' patients (p = 0.0035). These results are consistent with a previous observation made in Finnish T2DM patients. Moreover, assessing the haplogroup distribution in 'DP' versus 'HP' patients having diabetic siblings revealed that haplogroup J1 was virtually absent in the 'HP' group."] |
['Thiamine is an essential component of cellular metabolism, and lack of this vitamin results in a potentially life-threatening biochemical lesion. The stress of surgery and critical disease depletes electrolytes, minerals, and essential biochemical substrates. We hypothesized that critical illness (represented by major surgery) would result in decreased thiamine levels over time.', 'We performed a prospective, observational study of serial thiamine levels of 15 patients who underwent non-emergent coronary artery bypass graft surgery. The primary endpoint was change in thiamine levels from before to immediately after surgery. Secondary endpoints included change in thiamine levels from presurgical to 6- and 24-h time points.', 'Of the 15 study patients, 1 did not have a plasma thiamine measurement at time 0 because of laboratory error and could not be accounted for in paired comparisons over time. Plasma thiamine levels decreased significantly from before to after coronary artery bypass grafting (P=0.0004). In addition, there was a statistically significant decrease in thiamine levels from before surgery to 24h (P=0.003).'] |
['There are conflicting data regarding the incidence and factors implicated in the spontaneous clearance of hepatitis C virus (HCV) after acute infection. The aim of this study was to determine the epidemiological factors that predict the resolution of acute HCV infection without therapy in patients with human immunodeficiency virus (HIV) infection.', 'We conducted a retrospective, multivariate analysis of epidemiological data from HIV-infected patients presenting from 2000 to 2007 with evidence of past or present HCV infection. Data were collected from one American and two European HIV treatment clinics. A final cohort of 769 HIV-infected patients referred for treatment with available test results for antibody to HCV, HCV RNA, and hepatitis B surface antigen were included for the analysis. We calculated spontaneous clearance rates based on race, geographical location, gender, transmission risk factors, and hepatitis B virus coinfection.', 'Patients who admitted to a history of injection drug use spontaneously cleared the HCV infection significantly less often (11.6%) than those in whom sexual transmission was the presumed route of HCV infection (21.9%) (p=0.004). This difference was more pronounced when heterosexual contact as the source of infection was analyzed separately. Multivariate analysis identified heterosexual HCV transmission (OR 2.81, 95% CI 1.55-5.09) and hepatitis B surface antigen carrier status (OR 10.3, 95% CI 4.29-24.73) as independent factors predicting spontaneous HCV clearance. No differences according to gender, race or geographical origin were observed.'] |
['We have shown previously that the metalloproteinase inhibitor, BB-94, prolongs survival and attenuates MMP-2 activity in a murine model of pancreatic cancer. The purpose of this study was to determine the effect of BB-94 on the activity and activation of MMP-2 by PANC-1 cells in vitro.', "The poorly differentiated pancreatic cancer cell line PANC-1 was stimulated in vitro with the phorbol ester PMA (20 nM) and grown in the presence of increasing doses of BB-94 (0, 40, 200, and 400 ng/ml) for 24 h. Activation of MMP-2 was determined by gel zymography. In a separate experiment detailing the effects of BB-94 on MMP-2 activity, PANC cells were stimulated for 24 h with PMA and run out on four separate zymograms, each incubated in the previously noted concentrations of BB-94. Using densitometry, band intensity on all gels was determined and compared for each concentration of BB-94. The Matrigel assay was used to determine BB-94's effect on the invasive potential of PANC cells at the previously studied concentrations. The presence of MT-MMP (a putative component of MMP-2 activation) was confirmed using Western blot in each group.", 'BB-94 inhibited the conversion of latent to active MMP-2 in a dose-dependent fashion. BB-94 also inhibited the activity of MMP-2 when run out on gel zymograms incubated with increasing concentrations of BB-94. Decreased activity and activation of MMP-2 by BB-94 were manifested by a significant reduction in the invasive potential of PANC as determined by the Matrigel assay. MT-MMP was universally present in each study group.'] |
['Recent studies have suggested that the kallikrein-kinin system regulates tissue fibrogenesis. We hypothesize that bradykinin (BK), the main effector peptide of this system, regulates hepatic fibrogenesis.', 'Kallikrein-kinin system components were studied by quantitative reverse-transcription polymerase chain reaction analysis, immunohistochemistry, and Western blotting. The effect of bradykinin on liver injury was studied by infusing saline or bradykinin (1 and 100 ng/kg/min) through a subcutaneous pump into carbon tetrachloride-treated rats and mice treated with Fas-stimulating antibody. Bradykinin effects were studied in cultured hepatic stellate cells (HSCs) and hepatocytes.', 'Bradykinin receptors and kallikrein-1 were detected in both normal and fibrotic human livers and HSCs. BK receptors were up-regulated in fibrotic livers and activated HSCs. Bradykinin infusion reduced liver damage, as indicated by decreased aminotransferase serum levels and reduced histologic necroinflammatory score without inducing changes in arterial pressure. Moreover, bradykinin attenuated hepatic fibrosis, as indicated by reduced collagen accumulation, smooth muscle alpha-actin content, as well as decreased pro-collagen-alpha1(I) and transforming growth factor-beta1 gene expression. Bradykinin infusion reduced hepatocellular apoptosis induced by anti-Fas-receptor antibody. HSCs responded to bradykinin with intracellular calcium mobilization. Bradykinin reduced procollagen-alpha1(I) and transforming growth factor-beta1 gene expression and induced matrix metalloproteinase-2 activation. Finally, BK induced prosurvival and proliferative intracellular signaling in primary hepatocytes.'] |
['Left ventricular hypertrophy (LVH) poses a great risk of cardiovascular morbidity and mortality in adults and may pose a serious risk in children. Adult studies have shown that renin-angiotensin-aldosterone system (RAAS) levels directly correlate with left ventricular mass index (LVMI). The purpose of this study is to explore race- and sex-related effects of the RAAS on LVMI in adolescents.', 'Data were collected from a sample of 89 blacks (44 girls, 45 boys) and 102 whites (40 girls, 62 boys) aged 15-19. Data collected included sex, age, body mass index (BMI), LVMI, baseline blood pressure, and levels of aldosterone and angiotensin II.', 'In black males, increased aldosterone levels correlated with decreased sodium excretion (r=\u2009-0.336, p=0.024), increased blood pressure (r=0.358, p=0.016), and increased LVMI (r=0.342, p=0.022). In black females, increased aldosterone levels correlated with increased baseline blood pressure (r=0.356, p=0.018). In white males, increased aldosterone correlated with decreased sodium excretion (r=\u2009-0.391, p=0.002). In white females, aldosterone levels correlated with increased baseline blood pressure (r=0.323, p=0.042) and decreased sodium excretion (r=\u2009-0.342, p=0.031).'] |
['To evaluate the role of hormonal contraceptives as a risk factor of high-risk human papillomavirus (HR-HPV), cervical intraepithelial lesions (CIN) and cervical cancer in our multi-center population-based LAMS (Latin American Screening) study.', 'A cohort study with >12,000 women from Brazil and Argentina using logistic regression to analyze the covariates of hormonal contraception (HOC - oral, injections, patches, implants, vaginal ring and progesterone intrauterine system) use followed by multivariate modeling for predictors of HR-HPV and CIN2+.', 'HR-HPV infection was a consistent risk factor of high-grade CIN in all three groups of women. The length of HOC use was not significantly related to high-grade squamous intraepithelial lesions (HSIL)+ Pap (p = 0.069), LSIL+ Pap (p = 0.781) or ASCUS+ (p = 0.231). The same was true with the length of HOC use and histology CIN3+ (p = 0.115) and CIN2+ (p = 0.515). Frequently, HOC users have previously shown more HPV-related lesions, as well as lower HPV prevalence if they were current smokers. But HOC use and time of usage were not independent risk factors of either HR-HPV infection or high-grade CIN using multiple logistic regressions.'] |
['Prostaglandin E2 (PGE2) and thromboxane B2 (TxB2) concentrations are elevated in the injured spinal cord for hours to days after injury. Treatment of animals with a selective cyclooxygenase-2 (COX-2) inhibitor has been shown to improve functional outcome in an animal model.', 'We sought to characterize the effects of COX-2 inhibition on prostaglandin concentrations in the spinal cord after injury.', 'A drug study was performed using 76 male Long Evans rats.', 'PGE2 and TxB2 concentrations were measured by enzyme immune assay.', 'Fifty-six rats were subject to spinal cord injury, and 4 rats served as sham controls. Twenty eight rats received 3 mg/kg of celebocid by means of an orogastric tube within 20 minutes after injury, and 28 received vehicle alone. The animals were sacrificed at time points between 2 and 72 hours after injury, and PGE2 and TxB2 levels were measured. A second study was performed using transcardiac saline perfusion in order to reduce intragroup variance in measured PGE2 and TxB2 levels. Sixteen animals underwent spinal cord injury. Animals were sacrificed at 4 and 24 hours after injury, and PGE2 and TxB2 levels were measured.', 'PGE2 and TxB2 concentrations were elevated after injury in all animals. Administration of celebocid resulted in a delayed reduction of PGE2 and TxB2 concentrations in the initial drug study. These results were not statistically significant. Transcardiac perfusion with normal saline reduced the intragroup variance. Using this technique, administration of celebocid resulted in a statistically significant reduction in PGE2 and TxB2 concentrations in the injured cord segment 4 and 24 hours after injury.'] |
['Development of urinary incontinence, for many women, occurs following menopause. Dietary phytoestrogens consumed over the long term may affect the contractile function and maintenance of the urinary bladder in post menopausal women. This study examined the muscarinic receptor mediated contractile responses in the rat isolated bladder in response to ovariectomy and long term dietary phytoestrogen consumption.', 'Ovariectomised or sham-operated female Wistar rats (8 weeks) were fed either normal rat chow (soy, phytoestrogens) or a non-soy (phytoestrogen free) diet. Bladders were dissected from rats at 12, 24 and 52 weeks of age and placed in 25 ml organ baths filled with McEwans solution.', 'The contractile response to carbachol, in 12 week old female rats did not change as a result of dietary phytoestrogens or ovariectomy (P>0.05). At 24 weeks of age, detrusor muscle strip responses to carbachol from non-soy fed ovariectomised rats were attenuated (P<0.05). At 52 weeks, bladder detrusor strip responses to carbachol were reduced in all treatment groups with the exception of the soy-fed sham operated rats.'] |
['Omega-3 polyunsaturated fatty acids (n-3 PUFA) have been reported to reduce the risk of sudden cardiac death presumed to be due to fatal ventricular arrhythmias, but their effect on atrial arrhythmias is unclear.', 'Patients (n=108) undergoing coronary artery bypass graft surgery were randomly assigned to receive 2 g/d n-3 PUFA or placebo (olive oil) for at least 5 days before surgery (median, 16 days; range, 12 to 21 days). Phospholipid n-3 PUFA were measured in serum at study entry and at surgery and in right atrial appendage tissue at surgery. Echocardiography was used to assess left ventricular function and left atrial dimensions. Postoperative continuous ECG monitoring (Lifecard CF) for 5 days or until discharge, if earlier, was performed with a daily 12-lead ECG and clinical review if patients remained in the hospital beyond 5 days. Lifecard recordings were analyzed for episodes of atrial fibrillation (AF) > or =30 seconds (primary outcome). Clinical AF, AF burden (% time in AF), hospital stay, and intensive care/high dependency care stay were measured as secondary outcomes. One hundred three patients completed the study (51 in the placebo group and 52 in the n-3 PUFA group). There were no clinically relevant differences in baseline characteristics between groups. n-3 PUFA levels were higher in serum and right atrial tissue in the active treatment group. There was no significant difference between groups in the primary outcome of AF (95% confidence interval [CI], -6% to 30%, P=0.28) in any of the secondary outcomes or in AF-free survival.'] |
['Hispanics are the fastest growing ethnicity of the US population and the largest subset includes those of Mexican origin. Hispanics, including Mexican Americans (MAs), consistently report less tobacco exposure than European Americans (EAs), but limited data are available regarding differences in the clinical characteristics, severity of airflow obstruction, and functional status between MAs and EAs with chronic obstructive pulmonary disease (COPD).', 'Participants in a community-based study of aging and frailty among MAs and EAs, San Antonio Longitudinal Study of Aging, underwent spirometry. Participants with spirometry values consistent with COPD by Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria are described here.', 'Thirty-four percent (248/721) of the participants who underwent spirometry had evidence of GOLD Stages 1-4 COPD. Significantly more MAs with COPD reported being never smokers compared to EAs with COPD. Among those with COPD who also smoked, MAs reported significantly less tobacco exposure than EAs (15.7 vs. 32.4 pack-years, respectively), but both groups had surprisingly similar severities of airflow obstruction. Additionally, MAs had worse functional status and perceived health than did EAs.'] |
['It has been substantiated that the quality of pleurodesis is reduced when non-steroidal anti-inflammatory drugs (NSAIDs) are used perioperatively. The effects of NSAID administration on the early inflammatory and fibrinolytic processes after mechanical pleurodesis were investigated in an established pig model.', 'Left-sided mechanical pleural abrasion was performed on 24 pigs assigned to either an NSAID or a control group. Pleural fluid and blood samples were analysed over a 24-hour period. Histological evaluation of neutrophil influx at the site of pleural abrasion was performed.', 'The volume of pleural effusion was significantly decreased in the diclofenac group at 10 and 24 h, and the protein content was significantly lower. The diclofenac group at 24 h had a diminished total number of white blood cells and a reduced content of transforming growth factor-β. Moreover, the diclofenac group had a reduced percentage of neutrophils at 6 h. Significantly increased levels of D-dimers and tissue plasminogen activator were measured at 6 h and of interleukin-10 at 24 h. Neutrophils at the site of pleural abrasion were significantly reduced.'] |
['Cancer cells exhibit two types of DNA methylation alterations: global DNA hypomethylation and site-specific CpG island promoter hypermethylation. Selected gene promoter hypermethylation in normal esophageal mucosae has attracted attention as a surrogate marker for the epigenetic field defect induced by smoking and/or drinking in esophageal squamous cell carcinoma (ESCC). However, the significance of global DNA hypomethylation for field cancerization remains unclear.', 'By using histologically normal esophageal mucosa samples from 109 ESCC cases and 20 autopsy cases without ESCCs, we measured long interspersed nucleotide element 1 (LINE-1) methylation levels by pyrosequencing, which correlates with global DNA methylation level.', 'LINE-1 methylation levels in normal esophageal mucosae of ESCC patients were significantly lower than those of autopsy individuals (P = 0.017). LINE-1 methylation of noncancerous mucosae ranged 68.3-93.0 on a 0-100 scale (mean 81.7, median 82.2, standard deviation 5.9). LINE-1 hypomethylation was significantly associated with smoking history (P = 0.014 for smoking duration; P = 0.0017 for number of cigarettes per day; P = 0.0002 for tobacco pack-year). LINE-1 methylation was not associated with alcohol drinking or age at diagnosis.'] |
['To study the inhibitory effect of chlorpromazine (Chl), verapamil, and aspirin on hepatocyte apoptosis induced by the cessation of phenobarbital (Phe) treatment in mice.', 'Liver DNA content, ratio of liver weight/body weight, DNA fragmentation, DNA electrophoresis, the end-labeling test (TUNEL), and the morphologic changes of liver cells as indices of liver mass and hepatocyte apoptosis were applied to investigate (1) the kinetic process of hepatocyte proliferation induced by Phe 75 mg.kg-1 i.p. and the regression of hyperplastic liver caused by withdrawal of Phe in mice, (2) the effect of Chl 25 mg.kg-1, verapamil 50 mg.kg-1 or aspirin 60 mg.kg-1 i.p. on mouse hepatocyte apoptosis, and (3) the time course of effects of Chl on the regression of liver size and DNA fragmentation content after withdrawal of Phe.', 'The process of hepatocyte proliferation and regression induced by administration and withdrawal of Phe in mice consisted of 4 phases: proliferation, plateau, rapid regression, and slow regression phases. In the rapid regression phase, the typic changes of hepatocyte apoptosis were found, which was prevented in early period by the Ca(2+)-calmodulin antagonist Chl, but not by verapamil or aspirin.'] |
['Coherent averaging is a technique to recover the response to repetitively applied stimuli when that response is embedded in random noise. We derived novel indices for left ventricular dyssynchrony estimation from volume-catheter signals using coherent averaging procedure: mechanical dyssynchrony (DYSCoh) internal flow fraction (IFFCoh) and mechanical dispersion (DISPCoh). The percentage power of non-repetitive components in the volume signals (ResTotAvg) was also estimated. The aims of the study were to evaluate the indices, characterizing repetitive and non-recurrent components of the conductance-volume signals, and to assess the ability of these indices to detect the changes in dyssynchrony induced by biventricular pacing (BIV).', 'We compared the results obtained in 20 heart failure patients indicated to BIV (HF Group) during spontaneous conduction with the results from 12 patients with preserved ventricular function (non-HF Group), and with those obtained during BIV.', 'DISPCoh and ResTotAvg were significantly different in HF compared to non-HF group, and identified HF patients with high accuracy (area under curve at ROC analysis > 0.8). These indices also demonstrated significant differences after BIV (p = 0.047 and p = 0.037 respectively) and their baseline values correlated with the acute increase of stroke volume (r = 0.64 and r = 0.78, both with p < 0.005).'] |
['Cerebral microbleeds (CMBs) are associated with various pathologies of the cerebral small vessels according to their distribution (i.e., cerebral amyloid angiopathy or hypertensive angiopathy). We investigated the association between CMB location and kidney function in acute ischemic stroke patients.', 'We enrolled 1669 consecutive patients with acute ischemic stroke who underwent gradient-recalled echo brain magnetic resonance imaging. Kidney function was determined using the estimated glomerular filtration rate (eGFR). CMBs were classified into strictly lobar, strictly nonlobar (i.e., only deep or infratentorial), and a combination of both lobar and nonlobar. Multinomial logistic regression analyses were used to determine the factors associated with the existence of CMBs according to their location.', 'The patients were aged 66±12 years (mean±standard deviation), and 61.9% (1033/1669) of them were male. CMBs were found in 27.0% (452/1669) of the patients. The stroke subtypes of small-artery occlusion and cardioembolism occurred more frequently in those with strictly nonlobar CMBs (10.8%) and strictly lobar CMBs (48.8%), respectively. The mean eGFR was lower in the strictly nonlobar CMBs group (72±28 mL/min/1.73 m(2)) and the both lobar and nonlobar CMBs group (72±25 mL/min/1.73 m(2)) than in the no-CMBs group (86±29 mL/min/1.73 m(2)). Multivariate multinomial logistic regression revealed that eGFR <60 mL/min/1.73 m(2) was independently related to strictly nonlobar CMBs (odds ratio=2.63, p=0.001).'] |
['To assess the expression of Ki67 as prognosticator in rectal/recto sigmoid cancer.', 'Samples from 146 patients with rectal and recto sigmoid cancer were studied for expression of Ki67 and its prognostic significance in comparison with clinico-pathological predictors of survival. Formalin-fixed, paraffin-embedded tissues from 6 (4.1%) patients with T1, 26 (17.8%) with T2, 94 (64.4%) with T3, and 20 (13.7%) with T4 tumors were studied. Ki67 expression was determined immunohistochemically. Samples were divided according to mean value into high (>40%) and low (< or =40%) expression. Areas of extensive proliferation (>50%) were defined as "hot spot" areas.', 'Hot spot areas were present in samples regardless of histopathological grade. Lower TNM and Dukes stage and higher expression of Ki67 and presence of Ki67 hot spot areas in histopathological samples were associated with better survival, whereas no association was observed with histopathological grade (P = 0.78). In Cox multivariate regression analysis, significant prognostic factors were Dukes stage (P<0.001), presence of lymph node metastases (P = 0.015), age (P = 0.035) and presence of Ki67 hot spot areas (P = 0.044).'] |
['To determine the effect of routine intravenous (IV) administration set changes on central venous catheter (CVC) colonization and catheter-related bacteremia.', 'Prospective, randomized, controlled trial.', 'Eighteen-bed intensive care unit (ICU) in a large metropolitan hospital.', 'Two hundred fifty-one patients with 404 chlorhexidine gluconate and silver sulfadiazine-coated multi-lumen CVCs.', 'CVCs inserted in the ICU and in situ on day 4 were randomized to have their IV administration sets changed on day 4 (n = 203) or not at all (n = 201). Use of fluid containers and blood product administration sets was limited to 24 hours. CVCs were removed when not required, infection was suspected, or in place on day 7. Catheter cultures were performed on removal by blinded laboratory staff. Catheter-related bacteremia was diagnosed by a blinded intensivist using strict definitions. Data were collected regarding catheter duration, site, Acute Physiology and Chronic Health Evaluation (APACHE) II score, patient age, diagnosis, hyperglycemia, hypoalbuminemia, immune status, number of fluid containers and IV injections, and administration of propofol, blood, total parenteral nutrition, or lipid infusion.', 'There were 10 colonized CVCs in the group receiving a set change and 19 in the group not receiving one. This difference was not statistically significant on Kaplan-Meier survival analysis. There were 3 cases of catheter-related bacteremia per group. Logistic regression found that burns diagnosis and increased ICU stay significantly predicted colonization.'] |
['Centronuclear myopathy (CNM) is a rare congenital myopathy characterized by prominence of central nuclei on muscle biopsy. CNM has been associated with mutations in MTM1, DNM2, and BIN1 but many cases remain genetically unresolved. RYR1 encodes the principal sarcoplasmic reticulum calcium release channel and has been implicated in various congenital myopathies. We investigated whether RYR1 mutations cause CNM.', 'We sequenced the entire RYR1 coding sequence in 24 patients with a diagnosis of CNM from South Africa (n = 14) and Europe (n = 10) and identified mutations in 17 patients. The most common genotypes featured compound heterozygosity for RYR1 missense mutations and mutations resulting in reduced protein expression, including intronic splice site and frameshift mutations.', 'The high incidence in South African patients (n = 12/14) in conjunction with recurrent RYR1 mutations associated with common haplotypes suggested the presence of founder effects. In addition to central nuclei, prominent histopathological findings included (often multiple) internalized nuclei and type 1 fiber predominance and hypotrophy with relative type 2 hypertrophy. Although cores were not typically seen on oxidative stains, electron microscopy revealed subtle abnormalities in most cases. External ophthalmoplegia, proximal weakness, and bulbar involvement were prominent clinical findings.'] |
['The aim of this study was to compare carcinoembryonic antigen levels with detection of messenger ribonucleic acid coding for the tumor-associated antigen L6 in patients with colorectal cancer. Not only are carcinoembryonic antigens expressed by the corresponding tumor cell, but the messenger ribonucleic acid of tumor-associated antigens, in contrast, is produced exclusively by viable tumor cells.', 'L6 messenger ribonucleic acid was determined by reverse-transcription polymerase chain reaction. Carcinoembryonic antigen was measured by the enzyme-linked immunosorbent assay technique, with a cutoff value of 40 microg/l. Blood serum was sampled from 187 patients with colorectal cancer. Statistical significance was calculated with the McNemar chi-squared test.', 'Preoperatively, 79 percent of patients in all stages were positive for L6 messenger ribonucleic acid, whereas only 35 percent had elevated carcinoembryonic antigen titers (P < 0.001). In Dukes A tumors, 84.9 percent of patients were positive for L6 messenger ribonucleic acid, whereas carcinoembryonic antigen was elevated in only 16.9 percent of patients. Only in Dukes D tumors did the enzyme-linked immunosorbent assay for carcinoembryonic antigen exhibit the same sensitivity as reverse-transcription polymerase chain reaction for L6 messenger ribonucleic acid. Recurrence was detected significantly earlier by reverse-transcription polymerase chain reaction for L6 messenger ribonucleic acid than by enzyme-linked immunosorbent assay for carcinoembryonic antigen.'] |
['To evaluate gut microbial dysbiosis in two visceral hypersensitive models in comparison with irritable bowel syndrome (IBS) patients and to explore the extent to which these models capture the dysbiosis of IBS patients.', 'Visceral hypersensitivity was developed using the maternal separation (MS) rat model and post-inflammatory rat model. The visceral sensitivity of the model groups and control group was evaluated using the abdominal withdraw reflex score and electromyography in response to graded colorectal distention. The 16S ribosomal RNA gene from fecal samples was pyrosequenced and analyzed. The correlation between dysbiosis in the microbiota and visceral hypersensitivity was calculated. Positive findings were compared to sequencing data from a published human IBS cohort.', 'Dysbiosis triggered by neonatal maternal separation was lasting but not static. Both MS and post-inflammatory rat fecal microbiota deviated from that of the control rats to an extent that was larger than the co-housing effect. Two short chain fatty acid producing genera, Fusobacterium and Clostridium XI, were shared by the human IBS cohort and by the maternal separation rats and post-inflammatory rats, respectively, to different extents. Fusobacterium was significantly increased in the MS group, and its abundance positively correlated with the degree of visceral hypersensitivity. Porphyromonadaceae was a protective biomarker for both the rat control group and healthy human controls.'] |
['Several groups have achieved graft acceptance in the concordant hamster to rat model by using a combination of anti-proliferative drugs and conventional immunosuppressive therapy. However, such aggressive treatment often leads to the recipient dying with a functional xenograft, as a result of opportunistic infections. This study aimed to investigate the effects of a short course of therapy with an anti-MHC class II monoclonal antibody treatment (chimeric OX6 [cOX6]) in combination with cyclosporin A (CyA) in a concordant hamster-to-rat xenograft model.', 'Rats receiving hamster cardiac xenografts were given CyA or cOX6 alone or in combination and were monitored daily to assess the effect of treatment on graft survival. Additional studies monitored the effect of treatment on the production of cytolytic anti-hamster antibodies by the recipient and the deposition of immunoglobulin (Ig)M and complement factors within the xenograft.', 'Treatment with CyA only had no effect on graft survival, whereas treatment with cOX6 increased graft survival time by 2 days. The median graft survival time for cOX6+CyA was 76 days. cOX6 treatment of rats having undergone transplants inhibited the rise in cytotoxic anti-hamster antibodies in peripheral blood until day 5, whereas combination therapy completely inhibited anti-hamster antibody formation. Fluorescence-activated cell sorter analysis showed treatment with cOX6 significantly reduced circulating B cell numbers until day 5. Anti-MHC class II treatment also markedly reduced the deposition of both IgM and C3. Anti-MHC class II treatment with CyA gives long term survival in concordant xenografts without severe side effects.'] |
['Infection is an independent risk factor for adverse outcome in stroke patients. The risk of developing an infection in this setting is partly related to a stroke-induced immunodepression, in which a shift to a predominant Th2 (immunosuppressive) phenotype has been postulated to play a major role. Our aim was to study whether clinical variables or changes in plasma cytokine expression can predict poststroke infections.', 'Medical records of 92 stroke patients were reviewed, and the baseline concentration of cytokines from the Th1/Th2 system was determined. Clinical and serological predictors of incident infections and their prognostic significance were sought by means of univariate and multivariate analysis, and two predictive models for developing an infection were constructed by combining independent predictors (strictly clinical in one, and both clinical and serological in the other) for this outcome. The improvement conferred by the addition of immunological markers to the clinical model was assessed by comparing their respective ROC curves and by improvement (Net Reclassification Index and Integrated Discriminator Improvement) analysis.', 'Nineteen patients (20.7% of the study sample) developed an infection. Ongoing antiplatelet therapy at symptom onset (OR 0.02, 95% CI 0.001-0.23, p = 0.001), diabetes mellitus (OR 9.96, 95% CI 1.32-75.29, p = 0.03), IL-13 level <33 pg/ml (OR 84.16, 95% CI 2.53-2795.18, p = 0.01) and interferon-γ level >8.4 pg/ml (OR 60.17, 95% CI 1.78-2037.23, p = 0.02) were independently associated with the development of infections during hospital admission. The combined regression model predicted infection with an accuracy of 93.4%, an improvement in the predictive capacity of 17% (p < 0.001). Infection was associated with a worse neurological status at hospital discharge (median NIHSS score 11 (6-18) vs. 4 (1-11.5), p = 0.014).'] |
['The bronchial epithelium is exposed to reactive oxygen species (ROS) derived from cigarette smoke, air pollutants and activated leucocytes. Glutathione (GSH) prevents ROS-mediated loss of cell function, tissue injury and inflammation, and its synthesis is regulated by gamma-glutamylcysteine synthetase (gamma-GCS). However, the capacity of bronchial epithelial cells to adapt to oxidative stress and the mechanisms involved are not known.', 'To investigate the effects of oxidative stress on the regulation of GSH synthesis in human bronchial epithelial (NCI-H292) cells.', 'NCI-H292 cells were exposed to menadione and intracellular GSH concentrations were measured by spectrophotometry. gamma-GCS activity was measured by HPLC assay and changes in gamma-GCS mRNA by Northern blotting.', 'Exposure to menadione (MQ, 10-200 microm, 30-120 min) decreased total cellular GSH content, measured immediately after exposure to MQ. However, GSH content measured 6-12 h after withdrawal of the oxidant stress (MQ, 50 microm, 30 min), increased c. two fold over baseline levels (P < 0.001). gamma-GCS activity measured 6 h (21.7 +/- 3.4 nmol/min/mg, SD, n = 5, P < 0.01) or 12 h (23.2 +/- 4.6, P < 0.001) after MQ treatment was also significantly increased compared with untreated cells (12.8 +/- 1.0). Similarly, gamma-GCS mRNA expression increased 1.3-1.6-fold relative to GAPDH mRNA, 3-6 h after MQ treatment. The MQ-induced increase in gamma-GCS mRNA expression was completely inhibited by actinomycin D.'] |
['Ureteral stents are susceptible to biofilm formation and crystal deposition, especially in stone formers. To identify proteins responsible for this accumulation, we compared conditioning film proteomes obtained from human ureteral stents with and without encrustation.', 'Twenty-seven Bard Inlay hydrophilic ureteral stents were removed after ureteroscopy. Stent encrustation was quantified by visual analog score 0 (none) to 4 (heavy) and further categorized as nonencrusted (scores 0 and 1; n = 22) or encrusted (scores 2, 3, and 4; n = 5). Stent conditioning film was sampled and digested with trypsin, and peptide tandem mass spectrometry data were acquired using liquid chromatography. After protein identification, unconditional exact tests were used to compare categorical variables versus encrustation outcome. Stone analysis and follow-up metabolic urine profiles were examined to identify additional risk factors for stent encrustation.', 'More than 300 unique proteins with >95% confidence were identified. Proteins alpha-1 anti-trypsin, Ig kappa, IgH G1, and histone H2b and H3a were found to be highly associated with stent encrustation (p < 0.05), while Tamm-Horsfall protein and histone H2a were found to have a marginal association (p < 0.1). Patients with early stent encrustation were more likely to have mixed stone analysis (p = 0.03) and low urinary volumes (p < 0.01).'] |
['Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary arteriopathy caused by mutations of the Notch3 gene. The disease is characterized by T2-hyperintense lesions (subcortical white matter lesions), T1-hypointense lesions (lacunar lesions), and T2*-weighted gradient-echo (GE) lesions (cerebral microhemorrhages [CMs]) visualized on clinical MRI sequences and is considered as a model of "pure" subcortical ischemic vascular dementia. Although numerous studies have investigated the impact of white matter lesions in patients with CADASIL, the clinical importance of lacunar lesions remains unknown. Our purpose was to examine the influence of the visible MRI markers in the disease, including the load of lacunar lesions on cognitive impairment and disability in CADASIL.', 'We collected clinical data from 147 consecutive patients enrolled in an ongoing two-center prospective cohort study. Degree of disability was assessed by modified Rankin scale and Barthel index. Degree of cognitive impairment was assessed by Mattis Dementia Rating Scale and Mini-Mental Status Examination. T1-weighted, fluid-attenuated inversion recovery, and GE images were obtained on a 1.5-T MRI. Volume and location of lacunar lesions, white matter hyperintensities (WMHs), and CMs were assessed.', 'There was a significant independent association between age, volume of lacunar lesions, and global cognitive function scales when analyzed in a multivariable model. In contrast, WMHs and CMs had no independent influence on cognitive function. Disability in this cohort was associated with volume of lacunar lesions, CMs, systolic blood pressure, and age but not with WMHs.'] |
['Some psychotropic drugs are connected with prolongation of QT interval, increased risk of cardiac arrhythmias and greater incidence of sudden death, especially when used in combination. Concomitant use of antipsychotics and antidepressants is not rare in our clinical practice. The study compares the length of QT interval in patients on monotherapy with an antipsychotic or an antidepressant and patients taking polytherapy (an antipsychotic agent combined with an antidepressant).', "Sixty-one hospitalized women who met the ICD-10 criteria for schizophrenia, schizoaffective psychosis, delusional disorder and mood disorder were included in the study. The monotherapy group was consisted of thirty-two women treated with an antipsychotic or an antidepressant while the polytherapy group was composed of twenty-nine women treated with an antipsychotic agent plus an antidepressant. Two electrocardiograms (ECGs) were obtained for each patient: the first was carried out before the treatment and the second after two weeks of treatment.Statistical analysis was carried out by SPSS program and included unpaired and paired t test and Fisher's exact test.", "Mean baseline QTc values did not differ between the groups (439 +/- 22 ms was the same value found in the both groups; unpaired t test, p > 0.5). Mean QTc intervals after two weeks of treatment were also similar (439 +/- 24 ms in the monotherapy group and 440 +/- 20 ms in the polytherapy group; unpaired t test, p > 0.5). Fisher's exact test did not reveal significant difference in the number of patients with borderline (451-470 ms) or prolonged (> 470 ms) QTc between groups, neither before treatment nor after two weeks of treatment. Twenty two women of the total of sixty one patients (36%) had QTc > 450 ms before applying therapy."] |
['An experimental approach was used to test human cadaveric spine specimens.', 'To assess the response of the whole lumbar spine to a compressive follower load whose path approximates the tangent to the curve of the lumbar spine.', 'Compression on the lumbar spine is 1000 N for standing and walking and is higher during lifting. Ex vivo experiments show it buckles at 80-100 N. Differences between maximum ex vivo and in vivo loads have not been satisfactorily explained.', 'A new experimental technique was developed for applying a compressive follower load of physiologic magnitudes up to 1200 N. The experimental technique applied loads that minimized the internal shear forces and bending moments, made the resultant internal force compressive, and caused the load path to approximate the tangent to the curve of the lumbar spine.', 'A compressive vertical load applied in the neutral lordotic and forward-flexed postures caused large changes in lumbar lordosis at small load magnitudes. The specimen approached its extension or flexion limits at a vertical load of 100 N. In sharp contrast, the lumbar spine supported a load of up to 1200 N without damage or instability when the load path was tangent to the spinal curve.'] |
['To evaluate the use of SKread, a vision test based on random word sequences that prevents the prediction of upcoming words by linguistic criteria and is simple to score in a clinical setting.', 'SKread combines the standardized format of the MNread test with sequences of random words and letters like the Pepper Visual Skills for Reading test. A total of 231 subjects (aged 16 to 97 years) participated. We report data from 136 eyes of subjects with a maculopathy and 65 with normal or near-normal vision. Test reliability was investigated on an additional 30 eye-healthy subjects. We tested visual acuity and reading performance for continuous text and random words monocularly. Reading speed and all errors made are reported.', 'Reading speed was always higher for continuous text than for random word sequences, even in normally sighted subjects for whom the median reading times per paragraph were 2.4 s (MNread) vs. 6.8 s (SKread). In patients with maculopathies, the medians were 4.2 s vs. 12.25 s. These differences were statistically significant. Number and type of errors made depended only negligibly on age and visual acuity. Patients with a dense scotoma right of fixation made more "right errors" by missing letters at the end of words, whereas those with a scotoma left of fixation made more "left errors" by missing letters at the beginning of words. The SKread test showed good test-retest repeatability.'] |
['Several clinical trials have suggested that adjuvant chemotherapy improves the survival of patients with resected gastric cancer, but the optimal time at which to initiate post-operative adjuvant chemotherapy has not been studied. This study investigated the association between time to adjuvant chemotherapy and survival in gastric cancer.', 'We retrospectively identified 266 patients with stage IB-IIIC gastric cancer who received fluorouracil-based adjuvant chemotherapy after radical gastrectomy. Overall survival (OS) was compared between patients grouped according to time from surgery to adjuvant chemotherapy (<45 and ≥45 days). The Cox proportional hazards model was used to analyze the effects of time to initiation of chemotherapy and other clinical covariates on survival.', 'Of 266 patients, 141 (53%) started adjuvant chemotherapy within 45 days after surgery and 125 (47%) started adjuvant chemotherapy more than 45 days after surgery. The 3-year OS rates were 81.2 and 65.8% for patients starting chemotherapy within 45 days and after 45 days, respectively (p=0.006). Multivariate analysis identified early initiation of adjuvant chemotherapy, completion of the planned chemotherapy, and early-stage disease as favorable prognostic factors in terms of OS (p<0.05). Subgroup analysis suggested that starting chemotherapy within 45 days after surgery was associated with significant OS benefit compared with initiation of chemotherapy after 45 days from surgery in most subgroups.'] |
['The carcinogenic capacity of B[a]P/B[a]PDE is supported by epidemiologic studies. However, the molecular mechanisms responsible for B[a]P/B[a]PDE-caused lung cancer have not been well investigated. We evaluated here the role of novel target PHLPP2 in lung inflammation and carcinogenesis upon B[a]P/B[a]PDE exposure.', 'We used the Western blotting, RT-PCR, [(35)S]methionine pulse and immunohistochemistry staining to determine PHLPP2 downregulation following B[a]P/B[a]PDE exposure. Both B[a]PDE-induced Beas-2B cell transformation model and B[a]P-caused mouse lung cancer model were used to elucidate the mechanisms leading to PHLPP2 downregulation and lung carcinogenesis. The important findings were also extended to in vivo human studies.', "We found that B[a]P/B[a]PDE exposure downregulated PHLPP2 expression in human lung epithelial cells in vitro and in mouse lung tissues in vivo. The ectopic expression of PHLPP2 dramatically inhibited cell transformation upon B[a]PDE exposure. Mechanistic studies showed that miR-205 induction was crucial for inhibition of PHLPP2 protein translation by targeting PHLPP2-3'-UTR. Interestingly, PHLPP2 expression was inversely associated with tumor necrosis factor alpha (TNFα) expression, with low PHLPP2 and high TNFα expression in lung cancer tissues compared with the paired adjacent normal lung tissues. Additional studies revealed that PHLPP2 exhibited its antitumorigenic effect of B[a]P/B[a]PDE through the repression of inflammatory TNFα transcription."] |
['Ischemia-reperfusion injury (IRI) of renal grafts may cause remote organ injury including lungs. The authors aimed to evaluate the protective effect of xenon exposure against remote lung injury due to renal graft IRI in a rat renal transplantation model.', 'For in vitro studies, human lung epithelial cell A549 was challenged with H2O2, tumor necrosis factor-α, or conditioned medium from human kidney proximal tubular cells (HK-2) after hypothermia-hypoxia insults. For in vivo studies, the Lewis renal graft was stored in 4°C Soltran preserving solution for 24 h and transplanted into the Lewis recipient, and the lungs were harvested 24 h after grafting. Cultured lung cells or the recipient after engraftment was exposed to 70% Xe or N2. Phospho (p)-mammalian target of rapamycin (mTOR), hypoxia-inducible factor-1α (HIF-1α), Bcl-2, high-mobility group protein-1 (HMGB-1), TLR-4, and nuclear factor κB (NF-κB) expression, lung inflammation, and cell injuries were assessed.', 'Recipients receiving ischemic renal grafts developed pulmonary injury. Xenon treatment enhanced HIF-1α, which attenuated HMGB-1 translocation and NF-κB activation in A549 cells with oxidative and inflammatory stress. Xenon treatment enhanced p-mTOR, HIF-1α, and Bcl-2 expression and, in turn, promoted cell proliferation in the lung. Upon grafting, HMGB-1 translocation from lung epithelial nuclei was reduced; the TLR-4/NF-κB pathway was suppressed by xenon treatment; and subsequent tissue injury score (nitrogen vs. xenon: 26 ± 1.8 vs. 10.7 ± 2.6; n = 6) was significantly reduced.'] |
['Clinical trials in early breast cancer have suggested that benefits of adjuvant bone-targeted treatments are restricted to women with established menopause. We developed models that mimic pre- and postmenopausal status to investigate effects of altered bone turnover on growth of disseminated breast tumor cells. Here, we report a differential antitumor effect of zoledronic acid (ZOL) in these two settings.', 'Twleve-week-old female Balb/c-nude mice with disseminated MDA-MB-231 breast tumor cells in bone underwent sham operation or ovariectomy (OVX), mimicking the pre- and postmenopausal bone microenvironment, respectively. To determine the effects of bone-targeted therapy, sham/OVX animals received saline or 100 μg/kg ZOL weekly. Tumor growth was assessed by in vivo imaging and effects on bone by real-time PCR, micro-CT, histomorphometry, and measurements of bone markers. Disseminated tumor cells were detected by two-photon microscopy.', 'OVX increased bone resorption and induced growth of disseminated tumor cells in bone. Tumors were detected in 83% of animals following OVX (postmenopausal model) compared with 17% following sham operation (premenopausal model). OVX had no effect on tumors outside of bone. OVX-induced tumor growth was completely prevented by ZOL, despite the presence of disseminated tumor cells. ZOL did not affect tumor growth in bone in the sham-operated animals. ZOL increased bone volume in both groups.'] |
['To investigate whether the expression of p53 binding protein 1 (53BP1) has prognostic significance in a cohort of early-stage breast cancer patients treated with breast-conserving surgery and radiotherapy (BCS+RT).', 'A tissue microarray of early-stage breast cancer treated with BCS+RT from a cohort of 514 women was assayed for 53BP1, estrogen receptor, progesterone receptor, and HER2 expression by immunohistochemistry. Through log-rank tests and univariate and multivariate models, the staining profile of each tumor was correlated with clinical endpoints, including ipsilateral breast recurrence-free survival (IBRFS), distant metastasis-free survival (DMFS), cause-specific survival (CSS), recurrence-free survival (RFS), and overall survival (OS).', 'Of the 477 (93%) evaluable tumors, 63 (13%) were scored as low. Low expression of 53BP1 was associated with worse outcomes for all endpoints studied, including 10-year IBRFS (76.8% vs. 90.5%; P=.01), OS (66.4% vs. 81.7%; P=.02), CSS (66.0% vs. 87.4%; P<.01), DMFS (55.9% vs. 87.0%; P<.01), and RFS (45.2% vs. 80.6%; P<.01). Multivariate analysis incorporating various clinico-pathologic markers and 53BP1 expression found that 53BP1 expression was again an independent predictor of all endpoints (IBRFS: P=.0254; OS: P=.0094; CSS: P=.0033; DMFS: P=.0006; RFS: P=.0002). Low 53BP1 expression was also found to correlate with triple-negative (TN) phenotype (P<.01). Furthermore, in subset analysis of all TN breast cancer, negative 53BP1 expression trended for lower IBRFS (72.3% vs. 93.9%; P=.0361) and was significant for worse DMFS (48.2% vs. 86.8%; P=.0035) and RFS (37.8% vs. 83.7%; P=.0014).'] |
['We correlated the circadian rhythm of plasma arginine vasopressin and urine output profile to desmopressin response, presence or absence of an enuretic episode, and age and gender in children with nocturnal enuresis.', 'We studied 125 children 6 to 17 years old (mean age 10.4 +/- 3 years) with monosymptomatic nocturnal enuresis. Circadian inpatient studies were performed with standardized fluid intake, 7 blood sampling times and 6 urine collection periods. Subsequently, nocturnal urine volume was measured at home by diaper weighing for 4 weeks in 78 patients (2 weeks without treatment followed by 2 weeks of dose titration from 20 to 40 mug desmopressin at bedtime).', 'The circadian studies showed that all groups of patients had an attenuated arginine vasopressin rhythm, females generally had lower circadian plasma arginine vasopressin levels than males, desmopressin responders with enuresis during the study night had the largest nocturnal urine excretion rate and most pronounced arginine vasopressin deficiency, and nocturnal urine output was significantly greater during nights with enuresis than nights without. Part of this polyuria was caused by increased sodium excretion. The home recordings confirmed higher nocturnal urine volume on enuresis nights.'] |
['Experiments were designed to determine whether hyperkalemic crystalloid cardioplegic solution alters the hypoxic response of isolated segments of rabbit coronary arteries.', 'Coronary arteries were suspended in organ chambers to measure isometric force. We measured the coronary perfusion pressure at a constant flow rate in isolated Langendorff-perfused hearts. Coronary arteries and hearts were preserved in warm (37 degrees C) physiologic solution or in cold (10 degrees C) crystalloid cardioplegic solution.', 'In all groups of coronary arteries, the acetylcholine-induced relaxation before and after preservation was unchanged (n = 7). Hypoxia (15 mm Hg) caused an endothelium-dependent contraction, the amplitude of which did not change after cardioplegia. Conversely, in coronary arteries preserved in physiologic solution, hypoxic contraction amplitude decreased by 67% +/- 17%. In isolated hearts, hypoxic perfusion (15 mm Hg) induced a vasodilation. In all groups, the second hypoxic vasodilation was significantly greater (group 1, first hypoxic perfusion 2.8% +/- 2.8%, second hypoxic perfusion 18.2% +/- 7.1%; group 2, first hypoxic perfusion 6.8% +/- 1.5%, second hypoxic perfusion 29% +/- 9%).'] |
['QRS duration (QRSd) and prolonged corrected QT interval (QTc) are associated with ventricular arrhythmic events. This study was designed to determine whether CRT by means of biventricular pacing alters the QTc and QRSd, and whether such changes are related to the risk of sustained ventricular tachyarrhythmias (sVTA).', 'A total of 127 patients (102 men, mean age 63.9 +/- 8.9 years) with drug-resistant heart failure and QRS duration > or = 130 ms underwent CRT/CRT-ICD. The aetiology of the heart failure was ischaemic in 41 patients (32.3%). After a median follow-up of 24 months, 42 sVTA occurred in 35 patients (27.6%). Twenty-nine patients had a single sVTA, in five patients two sVTA and in one patient three sVTA occurred. The paced QTc was longer in sVTA patients (505 +/- 55 ms) compared with no sVTA patients (486 +/- 44 ms, P < or = 0.003). Similar responses for paced QRSd were observed (182 +/- 27 ms in sVTA patients vs 167 +/- 27 ms in no-sVTA patients, P < or = 0.03). This effect was independent from intrinsic QTc and QRSd and the aetiology of the heart failure. The mortality rate was significantly higher in patients with ventricular fibrillation and fast VT (P < or = 0.004) who experienced shock therapies. However, the sVTA were not the immediate cause of death.'] |
['To evaluate the discriminatory ability of maternal serum creatine kinase (SCK) as a test for ectopic pregnancy (EP).', 'Serum creatine kinase concentrations were obtained prospectively from symptomatic patients being evaluated for early abnormal pregnancy. Serum creatine kinase concentrations from all patients and from a subset of these patients with maternal serum beta-hCG concentrations < 6,500 mIU/mL (conversion factor to SI unit, 1.00) were analyzed with descriptive statistics, receiver operator characteristic (ROC) curve analysis, and calculations of predictive values.', 'A university hospital emergency room.', 'Fifty-six patients with intrauterine gestations (25 with beta-hCG concentrations < 6,500 mIU/mL) and 23 patients with EP (20 with beta-hCG concentrations < 6,500 mIU/mL) were studied.', 'For all patients and the subgroup with beta-hCG concentrations < 6,500 mIU/mL, mean SCK levels were not significantly different between ectopic and intrauterine gestations. For all patients and the subgroup with beta-hCG concentrations < 6,500 mIU/mL, the areas under the ROC curves did not demonstrate discriminatory ability of the SCK test. The highest positive predictive value of an elevated SCK for EP was 52% using the SCK concentration of 70 U/L, and this was seen in the subgroup of patients with beta-hCG values < 6,500 mIU/mL.'] |
["The cortisol-induced increase in von Willebrand factor (VWF) in Cushing's syndrome (CS) seems to depend on single nucleotide polymorphisms (SNPs) of the VWF promoter, haplotype 1 (-3268G/-2709C/-2661A/-2527G) being the susceptible pattern.", 'This study focused on a new variable region of the VWF promoter, the -2144(GT)(n) locus, to establish whether different GT-repeat lengths are also involved in modulating the cortisol-induced increase in VWF. Sixty-nine CS patients were investigated, divided into groups A (high VWF) and B (normal VWF).', 'Analysing the (GT)(n) locus revealed a similar allele distribution in CS patients and normal subjects, (GT)(n) variants ranging from 15 to 24 repeats and (GT)(19) and (GT)(21) being the two most represented. However, when groups A and B were analysed separately, a different allele distribution was observed: short GT-repeats (15-19, GT(S)) were more frequent in group A, long GT-repeats (20-24, GT(L)) in group B (p=0.01). About genotype distributions, (GT)(S)/(GT)(S) was higher in group A and rare in group B (22.5% and 3.4%, respectively), whereas (GT)(L)/(GT)(L) was higher in group B than in group A (55.2%, 27.5%) (p=0.021). Odds-ratio analysis revealed a risk of a cortisol-dependent increase in VWF three times higher for alleles (GT)(S) than for (GT)(L), and 13-fold for genotype (GT)(S)/(GT)(S) respect to (GT)(L)/(GT)(L).'] |
['Metabolic syndrome (MS) is considered a cause of abnormal deposition of fat into hepatocytes, which might be associated with hepatic steatosis or abnormal liver function.', 'The aim of this study was to explore the factors associated with MS and the relationship between MS and abnormal aspartate aminotransferase (AST), alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT) levels in Taiwanese subjects without chronic hepatitis B (CHB) or C (CHC).', 'We enrolled 2539 Taiwanese adults without CHB or CHC (age range: 16-88 years old) and investigated the factors related to MS using the NCEP-ATP (National Cholesterol Education Program-Adult Treatment Panel) III criteria; body mass index (BMI) was measured using Asia-Pacific criteria.', 'The prevalence rate of MS in Taiwanese adults without CHB or CHC was 16.9% using the modified ATP III criteria and 15.4% using the International Diabetes Federation criteria. Males had a significantly higher prevalence rate than females (P<0.001), and subjects with MS were significantly older and had significantly higher BMI values and AST, ALT and GGT levels (all P<0.001). In univariate analyses, the abnormality of liver function test results were related to gender, level of fasting sugar, systolic blood pressure, triglyceride, high-density lipoprotein, BMI and MS (all P<0.05). Multivariate analysis showed that the male gender, a higher BMI value and MS were related to abnormal liver function test results. The cutoff value for ALT in relation to MS is 31 IU l(-1) for male and 18 IU l(-1) for female.'] |
['Literature reports that surveillance imaging following endovascular aortic aneurysm repair (EVAR) gives rise to asymptomatic secondary interventions (SI) in 1.4-9% of cases. This retrospective study aimed to evaluate whether the modality of surveillance imaging influences the detection rate of asymptomatic SI.', "Two EVAR surveillance protocols were compared at the same vascular centre. Protocol I, performed from January 2003 to December 2006, consisted of colour duplex ultrasound scan (CDU) plus CT angiography (CTA) 1 month after procedure and every 6 months thereafter. Protocol II, performed from January 2007 to June 2010, consisted of CDU plus CTA 1 month after operation and CDU plus plain abdominal films (XR) every 6 months thereafter. In the second protocol, CTA was carried out only during follow-up in specific conditions. The term 'asymptomatic SI' was used when the necessity for SI was detected by imaging alone on an elective basis, prior to development of any symptoms.", 'Enrolment included 376 and 341 consecutive patients with a mean follow-up of 1148 days (range 1-3204 days) and 942 days (range1-1512 days) in Protocols I and II, respectively (p\xa0<\xa00.001). Freedom rates from aneurysmal rupture, freedom from SI and detection rate for asymptomatic SI at 3 years were 98.3% and 98.7% (p\xa0=\xa00.456), 82% and 83.5%(p\xa0=\xa00.876) and 8.8% (n\xa0=\xa033/376) and 8.5%(n\xa0=\xa025/341) (p\xa0=\xa00.49) in Protocols I and II, respectively. Estimated comparison of the costs, radiation exposure and contrast used at 3 years in Protocol I versus Protocol II showed that Protocol II allowed for a three-, four- and six fold reduction in overall costs, radiation exposure and contrast used, respectively (p\xa0<\xa00.0001).'] |
['Migraine headache attacks have been shown to be accompanied by significant prolongation of somatosensory temporal discrimination threshold values, supporting signs of disrupted sensorial processing in migraine. Chronic migraine is one of the most debilitating and challenging headache disorders with no available biomarker. We aimed to test the diagnostic value of somatosensory temporal discrimination for chronic migraine in this prospective, controlled study.', 'Fifteen chronic migraine patients and 15 healthy controls completed the study. Chronic migraine patients were evaluated twice, during a headache and headache-free period. Somatosensory temporal discrimination threshold values were evaluated in both hands. Duration of migraine and chronic migraine, headache intensity, clinical features accompanying headache such as nausea, photophobia, phonophobia and osmophobia, and pressure pain thresholds were also recorded.', 'In the chronic migraine group, somatosensory temporal discrimination threshold values on the headache day (138.8\u2009±\u200921.8 ms for the right hand and 141.2\u2009±\u200917.4 ms for the left hand) were significantly higher than somatosensory temporal discrimination threshold values on the headache free day (121.5\u2009±\u200913.8 ms for the right hand and 122.8\u2009±\u200912.6 ms for the left hand, P\u2009=\u2009.003 and P\u2009<\u2009.0001, respectively) and somatosensory temporal discrimination thresholds of healthy volunteers (35.4\u2009±\u20095.5 ms for the right hand and 36.4\u2009±\u20095.4 ms for the left hand, P\u2009<\u2009.0001 and P\u2009<\u2009.0001, respectively). Somatosensory temporal discrimination threshold values of chronic migraine patients on the headache free day were significantly prolonged compared to somatosensory temporal discrimination threshold values of the control group (121.5\u2009±\u200913.8 ms vs 35.4\u2009±\u20095.5 ms for the right hand, P\u2009<\u2009.0001 and 122.8\u2009±\u200912.6 ms vs 36.4\u2009±\u20095.4 ms for the left hand, P\u2009<\u2009.0001). Somatosensory temporal discrimination threshold values of the hand contralateral to the headache lateralization (153.3\u2009±\u200913.7 ms) were significantly higher (P\u2009<\u2009.0001) than the ipsilateral hand (118.2\u2009±\u200911.9 ms) in chronic migraine patients when headache was lateralized. The headache intensity of chronic migraine patients rated with visual analog score was positively correlated with the contralateral somatosensory temporal discrimination threshold values.'] |
['Advanced glycation end products (AGEs) are produced by glycoxidation and lipid peroxidation. AGEs induce oxidative stress and inflammation, and accumulate in tubular cells after kidney transplantation. We hypothesize that the AGE formation blocker aminoguanidine (AG) reduces AGE formation and improves renal transplant function.', 'Fisher 344 kidneys were orthotopically transplanted into Lewis recipients. Recipients were treated with AG (100 mg/kg/day), candesartan (CAND; 5mg/kg/day), or vehicle (VEH) for 24 weeks. The major non-cross linking AGE N(ε)-carboxymethyllysine (CML) was measured post-transplantation with gas chromatography-tandem mass spectrometry or immunohistochemistry. As a marker of systemic lipid peroxidation 8-isoprostane was measured by ELISA. We determined intra-arterial blood pressure, heart weight/body weight ratio, size of cardiomyocytes and cardiac hypertrophy as assessed by echocardiography. For biochemical evaluation of cardiac and renal fibrosis we measured hydroxyproline content.', 'AG significantly reduced serum CML and 8-isoprostane, but did not reduce signs of chronic allograft nephropathy (CAN) or blood pressure. AG did not alter tubular AGE accumulation. AG reduced heart weight/body weight ratio (AG: 2.7 ± 0.1g/kg; CAND: 2.2 ± 0.1, VEH: 3.0 ± 0.4 g/kg), size of cardiomyocytes (P < 0.05) and showed a tendency to reduce cardiac hypertrophy (wall volume average radial AG 7.072 ± 0.83 cm(3) vs. CAND 6.841 ± 0.66 cm(3) vs. VEH 7.839 ± 0.74 cm(3)).'] |
['Gastroesophageal reflux disease is a condition frequently associated with esophagitis and motor abnormalities. Recent evidence suggests that proinflammatory cytokines, such as interleukin (IL)-1beta and IL-6, may be implicated because they reduce esophageal muscle contractility, but these results derive from in vitro or animal models of esophagitis. This study used human esophageal cells and tissues to identify the cellular source of cytokines in human esophagitis investigate whether cytokines can be induced by gastric refluxate, and examine whether esophageal tissue- or cell-derived mediators affect muscle contractility.', 'Endoscopic mucosal biopsy specimens were obtained from patients with and without esophagitis, organ-cultured, and undernatants were assessed for cytokine content. The cytokine profile of esophageal epithelial, fibroblast, and muscle cells was analyzed, and esophageal mucosa and cell products were tested in an esophageal circular muscle contraction assay.', 'The mucosa of esophagitis patients produced significantly greater amounts of IL-1beta and IL-6 compared with those of control patients. Cultured esophageal epithelial cells produced IL-6, as did fibroblasts and muscle cells. Epithelial cells exposed to buffered, but not denatured, gastric juice produced IL-6. Undernatants of mucosal biopsy cultures from esophagitis patients reduced esophageal muscle contraction, as did supernatants from esophageal epithelial cell cultures.'] |
['New therapies for inflammatory bowel disease (IBD) are highly desirable. As apolipoprotein (apo)A-I mimetic peptides are beneficial in several animal models of inflammation, we hypothesized that they might be effective at inhibiting murine colitis.', 'Daily injections of 5A peptide, a synthetic bihelical apoA-I mimetic dissolved in PBS, or PBS alone were administered to C57BL/6 mice fed 3% (w v(-1) ) dextran sodium sulfate (DSS) in drinking water or healthy controls.', 'Daily treatment with 5A peptide potently restricted DSS-induced inflammation, as indicated by improved disease activity indices and colon histology, as well as decreased intestinal tissue myeloperoxidase levels and plasma TNFα and IL-6 concentrations. Additionally, plasma levels of monocyte chemoattractant protein-1 and the monocyte expression of adhesion-mediating molecule CD11b were down-regulated, pro-inflammatory CD11b(+) /Ly6c(high) monocytes were decreased, and the number of intestinal monocytes was reduced in 5A peptide-treated animals as determined by intravital macrophage-related peptide-8/14-directed fluorescence-mediated tomography and post-mortem immunhistochemical F4/80 staining. Intravital fluorescence microscopy of colonic microvasculature demonstrated inhibitory effects of 5A peptide on leukocyte adhesion accompanied by reduced plasma levels of the soluble adhesion molecule sICAM-1. In vitro 5A peptide reduced monocyte adhesion and transmigration in TNFα-stimulated monolayers of human intestinal microvascular endothelial cells. Increased susceptibility to DSS-induced inflammation was noted in apoA-I(-/-) mice.'] |
['Axillary block is popular technique in upper extremity surgery. Nerve stimulation is used for location of nerves to provide effective blockade. The advent of ultrasound imaging technique in regional anaesthesia has increased the accuracy of needle placement and local anaesthetic deposition around the nerve. The aim of this study is to find out if the nerve stimulation technique with ultrasound guidance has advantages over sole nerve stimulation technique. The outcome measures studied were onset of sensory and motor block, procedure time, number of skin puncture, vascular puncture and paresthesia during nerve stimulation.', 'This is a prospective randomized comparative study conducted in KMCTH from June 2009 to March 2010 on patients of American Society of Anaesthesiologist I and II requiring upper arm surgery under axillary block. The study comprised of two groups: ultrasound with nerve stimulation group (n=35) and nerve stimulation group (n=35). 24 ml of Bupivacaine 0.5% with injection Dexamethasone 4 mg was used to block the individual four nerves with 6 ml of the local anaesthetic solution per nerve namely ulnar, radial, median and musculocutaneous. The data were recorded by blinded observer. In case of partial block or block failure, the patients were supplemented with Fentanyl or subjected to laryngeal mask placement.', 'Demographic characteristics (age, weight) in either group were similar (p>0.05). The male and female ratio (M: F) in ultrasound with nerve stimulation group was 12:16. The ratio was 18:17 in nerve stimulation group. The onset of complete sensory block was earlier and the onset of motor block was faster in ultrasound with nerve stimulation group than in sole nerve stimulation group (p=0.001). Ultrasound guidance decreased the number of skin puncture during the nerve stimulation, p= 0.02. The incidence of paresthesia was encountered during nerve location (14%), which could be minimized using ultrasound (7%). The success rate of the block was 93% with ultrasound assistance. The procedure time was not different in both techniques. The surgery duration was not significant statistically in either of the group, p=0.715.'] |
['We evaluated the in vitro activity of posaconazole against nine Candida species using minimum fungicidal concentration (MFC) measurements and time-kill methods.', 'MFCs of posaconazole were determined for 209 clinical isolates (32 Candida albicans, 30 Candida glabrata, 21 Candida tropicalis, 29 Candida krusei, 28 Candida parapsilosis sensu stricto, 50 Candida inconspicua, 13 Candida kefyr, 3 Candida lusitaniae and 3 Candida guilliermondii) and 7 ATCC Candida strains. The following strains were tested in time-kill studies: 3 strains each of C. glabrata, C. kefyr, C. guilliermondii and C. lusitaniae; 2 C. tropicalis; 4 C. albicans; 4 C. inconspicua; 9 C. krusei; 12 C. parapsilosis; and 7 ATCC strains.', 'Posaconazole was fungicidal in both MFC and time-kill experiments (at 2 mg/L within 48 h in time-kill assays) against each C. krusei, C. inconspicua and C. lusitaniae strain and was fungistatic against each C. albicans, C. glabrata, C. tropicalis and C. guilliermondii strain. For the C. parapsilosis strains, posaconazole MFCs were <or=2 mg/L for 20 of the 28 isolates tested; however, in the time-kill tests, even at drug concentrations of 32-64 x MIC, posaconazole was fungistatic against all C. parapsilosis strains tested.'] |
['The impact of deep white matter lesions observed at the corona radiata on diffusion-weighted MRI (DWI-W lesions) on the clinical recovery of patients after tissue plasminogen activator (tPA) therapy is unclear. Our goal was to elucidate whether DWI findings before tPA could predict clinical recovery.', 'A total of 83 consecutive patients with hyperacute anterior circulation ischemic stroke were enrolled. All patients underwent MRI within 3 h and received intravenous tPA. The relationships among the Alberta Stroke Program Early CT Score (ASPECTS) on DWI (DWI-ASPECTS), DWI-W lesions, early dramatic improvement (> or =10-point reduction in the total National Institutes of Health Stroke Scale, NIHSS, score or a total NIHSS score of 0-2 after 24 h), early improvement (> or =4-point reduction in the total NIHSS score after 24 h) and worsening (> or =4-point increase in the total NIHSS score after 24 h) were assessed.', 'The median of the baseline DWI-ASPECTS value was 9 (range: 5-10), and DWI-W lesions were found in 36 patients (43%). Patients with early dramatic improvement had a shorter time from onset to tPA (116.1 +/- 34.9 vs. 133.2 +/- 33.1 min; p = 0.0281) and higher DWI-ASPECTS (medians: 9 vs. 9; p = 0.0568). DWI-W lesions were seen less frequently in patients with than without early dramatic improvement (26 vs. 54%; p = 0.0213). Multivariate logistic regression analysis demonstrated that absence of DWI-W lesions (OR: 1.80; 95% CI: 1.08-3.13; p = 0.0279), higher ASPECTS (OR: 1.56; 95% CI: 1.06-2.46; p = 0.0346) and shorter time from onset to tPA (OR: 0.98; 95% CI: 0.97-0.99; p = 0.0429) were independent predictors of early dramatic improvement.'] |
['Establishment and maintenance of epithelial cell\xa0polarity is regulated in part by signaling from adhesion receptors. Loss of cell polarity is associated with multiple pathologies including the initiation and progression of various cancers. The β1-integrin adhesion receptor plays a role in the regulation of cell polarity; however, the identity of the signaling pathways that modulate β1-integrin function and connect it to the regulation of polarity pathways remains largely unknown.', 'The present work identifies a role for Arg, a member of the Abl family nonreceptor tyrosine kinases, in the regulation of adhesive signals and epithelial cell polarity. In a three-dimensional cell culture model, activation of Arg kinase leads to a striking inversion of apical-basal polarity. In contrast, loss of Arg function impairs the establishment of a polarized epithelial cyst structure. Activated Arg kinase disrupts β1-integrin signaling and localization and impairs Rac1-mediated laminin assembly. Disruption of β1-integrin function by active Arg results in altered distribution of selected polarity complex components mediated in part by Rap1 GTPase signaling. Whereas polarity inversion is partially rescued by a constitutively active Rap1, Rac1-dependent laminin assembly is not, indicating that Rap1 and Rac1 signal independently during epithelial polarity.'] |
['The progestagenic milieu of pregnancy and oral contraceptive use is protective against epithelial ovarian cancer. A functional single nucleotide polymorphism in the promoter of the progesterone receptor (+331A) alters the relative abundance of the A and B isoforms and has been associated with an increased risk of endometrial and breast cancer. In this study, we sought to determine whether this polymorphism affects ovarian cancer risk.', 'The +331G/A polymorphism was genotyped in a population-based, case-control study from North Carolina that included 942 Caucasian subjects (438 cases, 504 controls) and in a confirmatory group from Australia (535 cases, 298 controls). Logistic regression analysis was used to calculate age-adjusted odds ratios (OR).', 'There was a suggestion of a protective effect of the +331A allele (AA or GA) against ovarian cancer in the North Carolina study [OR, 0.72; 95% confidence interval (95% CI), 0.47-1.10]. Examination of genotype frequencies by histologic type revealed that this was due to a decreased risk of endometrioid and clear cell cancers (OR, 0.30; 95% CI, 0.09-0.97). Similarly, in the Australian study, there was a nonsignificant decrease in the risk of ovarian cancer among those with the +331A allele (OR, 0.83; 95% CI, 0.51-1.35) that was strongest in the endometrioid/clear cell group (OR, 0.60; 95% CI, 0.24-1.44). In the combined U.S.-Australian data that included 174 endometrioid/clear cell cases (166 invasive, 8 borderline), the +331A allele was significantly associated with protection against this subset of ovarian cancers (OR, 0.46; 95% CI, 0.23-0.92). Preliminary evidence of a protective effect of the +331A allele against endometriosis was also noted in control subjects (OR, 0.19; 95% CI, 0.03-1.38).'] |
['Vitamin A plays a major role in lipid metabolism. Previously, we reported that chronic vitamin A feeding (129 mg/kg) for two months normalized the abnormally high plasma HDL-cholesterol (HDL-C) levels in hypercholesterolemic obese rats by upregulating the hepatic scavenger receptor class B type 1 (SR-BI) expression. In this report, we hypothesize that the administration of a dose less than 129 mg of vitamin A/kg would also be effective in lowering the plasma HDL-C levels in these rats.', 'Changes in the activity and expression of proteins related to RCT were analyzed together with blood parameters in five-month-old male lean and obese rats supplemented with 2.6 (control group), 26, 52 and 129 mg of vitamin A/kg as retinyl palmitate for 20 weeks.', 'Vitamin A supplementation in the obese rats decreased the plasma HDL-C levels with a concomitant increase in the hepatic SR-BI expression and lipase activity compared to that observed in the control diet-fed obese rats treated with 2.6 mg of vitamin A/kg diet. Furthermore, vitamin A supplementation at doses of 52 and 129 mg/kg diet reduced the plasma lecithin cholesterol acyltransferase activity and increased the hepatic ATP-binding cassette transporter protein A1 expression in the obese rats. Interestingly, most of these changes were not observed in the lean rats fed a vitamin A-enriched diet.'] |
['The epidermal growth factor receptor-targeted monoclonal antibody cetuximab (Erbitux) was recently introduced for the treatment of metastatic colorectal cancer. Treatment response is dependent on Kirsten-Ras (K-Ras) mutation status, in which the majority of patients with tumour-specific K-Ras mutations fail to respond to treatment. Mutations in the oncogenes B-Raf and PIK3CA (phosphoinositide-3-kinase) may also influence cetuximab response, highlighting the need for a sensitive, accurate and quantitative assessment of tumour mutation burden.', 'Mutations in K-Ras, B-Raf and PIK3CA were identified by both dideoxy and quantitative pyrosequencing-based methods in a cohort of unselected colorectal tumours (n=102), and pyrosequencing-based mutation calls correlated with various clinico-pathological parameters.', 'The use of quantitative pyrosequencing-based methods allowed us to report a 13.7% increase in mutation burden, and to identify low-frequency (<30% mutation burden) mutations not routinely detected by dideoxy sequencing. K-Ras and B-Raf mutations were mutually exclusive and independently associated with a more advanced tumour phenotype.'] |
['To test the effectiveness of, and explore interactions between, three interventions to prevent falls among older people.', 'A randomised controlled trial with a full factorial design.', 'Urban community in Melbourne, Australia.', '1090 aged 70 years and over and living at home. Most were Australian born and rated their health as good to excellent; just over half lived alone.', 'Three interventions (group based exercise, home hazard management, and vision improvement) delivered to eight groups defined by the presence or absence of each intervention.', 'Time to first fall ascertained by an 18 month falls calendar and analysed with survival analysis techniques. Changes to targeted risk factors were assessed by using measures of quadriceps strength, balance, vision, and number of hazards in the home.', 'The rate ratio for exercise was 0.82 (95% confidence interval 0.70 to 0.97, P=0.02), and a significant effect (P<0.05) was observed for the combinations of interventions that involved exercise. Balance measures improved significantly among the exercise group. Neither home hazard management nor treatment of poor vision showed a significant effect. The strongest effect was observed for all three interventions combined (rate ratio 0.67 (0.51 to 0.88, P=0.004)), producing an estimated 14.0% reduction in the annual fall rate. The number of people needed to be treated to prevent one fall a year ranged from 32 for home hazard management to 7 for all three interventions combined.'] |
['This paper introduces a seismocardiography based methodology of predicting the start and the end of diastole to be used in diastolic timed vibrations (DTV), which provides non-invasive emergency treatment of acute coronary thrombosis by applying direct mechanical vibrations to the patient chest during diastole of heart cycles. It is proposed that seismocardiogram (SCG), in combination with electrocardiogram (ECG), provides a new means of diastole prediction.', 'An accelerometer was placed on the sternum of 120 healthy participants and 22 ischemic heart patients to record precordial accelerations created by the heart. The accelerometer signal was used to extract SCG and phonocardiogram (PCG). Two independent trained experts annotated the extracted signals based on the timings of the start and end of diastole.', 'In the ischemic heart disease population by using 15 consecutive SCG cycles, the start and end of diastole was predicted in the upcoming cycles with 95 percentile error margin of 10.7 ms and 5.8 ms, respectively. These error margins were 7.4 ms and 3.5 ms, respectively, for normal participants.'] |
['Methane (CH(4)) is a potent greenhouse gas (GHG), having a global warming potential 21 times that of carbon dioxide (CO(2)). Methane emissions from agriculture represent around 40% of the emissions produced by human-related activities, the single largest source being enteric fermentation, mainly in ruminant livestock. Technologies to reduce these emissions are lacking. Ruminant methane is formed by the action of methanogenic archaea typified by Methanobrevibacter ruminantium, which is present in ruminants fed a wide variety of diets worldwide. To gain more insight into the lifestyle of a rumen methanogen, and to identify genes and proteins that can be targeted to reduce methane production, we have sequenced the 2.93 Mb genome of M. ruminantium M1, the first rumen methanogen genome to be completed.', 'The M1 genome was sequenced, annotated and subjected to comparative genomic and metabolic pathway analyses. Conserved and methanogen-specific gene sets suitable as targets for vaccine development or chemogenomic-based inhibition of rumen methanogens were identified. The feasibility of using a synthetic peptide-directed vaccinology approach to target epitopes of methanogen surface proteins was demonstrated. A prophage genome was described and its lytic enzyme, endoisopeptidase PeiR, was shown to lyse M1 cells in pure culture. A predicted stimulation of M1 growth by alcohols was demonstrated and microarray analyses indicated up-regulation of methanogenesis genes during co-culture with a hydrogen (H(2)) producing rumen bacterium. We also report the discovery of non-ribosomal peptide synthetases in M. ruminantium M1, the first reported in archaeal species.'] |
['Primary ovarian insufficiency (POI), or premature ovarian failure, results from ovarian follicle depletion with a consequent elevation of FSH levels before age 40 years. We identified a family in which 9 women in 3 consecutive generations developed menopause at approximately age 30 years. We hypothesized a genetic cause with a dominant mode of inheritance.', 'This was a family-based genetic study and a replicate group of women with POI.', 'The study was conducted at an academic medical center.', 'Seven affected women and an obligate carrier and 7 unaffected family members were genotyped. The genes of interest were also sequenced in 38 unrelated women with POI.', 'The DNA from 7 family members was subjected to whole-exome sequencing. The genotypes of interest were confirmed and genotypes of additional family members and unrelated women with POI were determined using Sanger sequencing.', 'A high-impact, deleterious variant that segregated appropriately with POI in the family was required.', 'A heterozygous stop codon (Ser429X) was identified in the eukaryotic translation initiation factor 4E nuclear import factor 1 (eIF4ENIF1) in the proband and all affected women but not in the unaffected family members. The chance that such a high-impact, deleterious variant would segregate appropriately among the affected and unaffected relatives by chance is very low (P < .05). There were no additional mutations identified in eIF4ENIF1 or eIF4E in 38 unrelated women with POI.'] |
['We evaluated effects of the nonpeptide angiotensin (ANG)-(1-7) analog AVE 0991 (AVE) on cardiac function and remodeling as well as transforming growth factor-beta1 (TGF-β1)/tumor necrosis factor-alpha (TNF-α) expression in myocardial infarction rat models.', 'Sprague-Dawley rats underwent either sham surgery or coronary ligation. They were divided into four groups: sham, control, AVE, and AVE+A-779 [[D-Ala(7) ]-ANG-(1-7), a selective antagonist for the ANG-(1-7)] group. After 4 weeks of treatment, the AVE group displayed a significant elevation in left ventricular fractional shorting (LVFS) (25.5 ± 7.3% vs. 18.4 ± 3.3%, P < 0.05) and left ventricular ejection fraction (LVEF) (44.8 ± 7.6% vs. 32.7 ± 6.5%, P < 0.05) when compared to the control group, but no effects on the left ventricular end-diastolic and end-systolic diameters (LVDd and LVDs, respectively) were observed. In addition, we found that the myocyte diameter (18 ± 2 μm vs. 22 ± 4 μm, P < 0.05), infarct size (42.6 ± 3.6% vs. 50.9 ± 4.4%, P < 0.001) and collagen volume fraction (CVF) (16.4 ± 2.2% vs. 25.3 ± 3.2%, P < 0.001) were significantly reduced in the AVE group when compared to the control group. There were no differences in LVFS, LVEF, myocyte diameter, and infarct size between the control and AVE+A-779 groups. AVE also markedly attenuated the increased mRNA expression of collagen I (P < 0.001) and collagen III (P < 0.001) and inhibited the overexpression of TGF-β1 (P < 0.05) and TNF-α (P < 0.05) compared to the control group.'] |
['Flaxseed, the richest source of mammalian lignan precursors, has previously been shown to reduce the growth of tumors in rats. This study examined, in a randomized double-blind placebo-controlled clinical trial, the effects of dietary flaxseed on tumor biological markers and urinary lignan excretion in postmenopausal patients with newly diagnosed breast cancer.', 'Patients were randomized to daily intake of either a 25 g flaxseed-containing muffin (n = 19) or a control (placebo) muffin (n = 13). At the time of diagnosis and again at definitive surgery, tumor tissue was analyzed for the rate of tumor cell proliferation (Ki-67 labeling index, primary end point), apoptosis, c-erbB2 expression, and estrogen and progesterone receptor levels. Twenty-four-hour urine samples were analyzed for lignans, and 3-day diet records were evaluated for macronutrient and caloric intake. Mean treatment times were 39 and 32 days in the placebo and flaxseed groups, respectively.', 'Reductions in Ki-67 labeling index (34.2%; P = 0.001) and in c-erbB2 expression (71.0%; P = 0.003) and an increase in apoptosis (30.7%; P = 0.007) were observed in the flaxseed, but not in the placebo group. No significant differences in caloric and macronutrient intake were seen between groups and between pre- and posttreatment periods. A significant increase in mean urinary lignan excretion was observed in the flaxseed group (1,300%; P < 0.01) compared with placebo controls. The total intake of flaxseed was correlated with changes in c-erbB2 score (r = -0.373; P = 0.036) and apoptotic index (r = 0.495; P < 0.004).'] |
['Innate immunity plays a role in controlling adaptive immune responses.', 'We investigated the clinical relevance of single nucleotide polymorphisms in 22 genes encoding innate, secreted, and signaling pattern recognition receptors in a total of 520 donor-recipient pairs of postmortem, human leukocyte antigen-DR-compatible kidney transplantations. Associations with rejection incidence were tested in an a priori randomized training set and validation set.', 'Polymorphisms in TLR-3 (rs3775296) in the recipients and in ficolin-2 (rs7851696; Ala258Ser) and C1qR1 (rs7492) in the donors showed the strongest association with severe rejection. In multivariate analysis, presence of the ficolin-2 Ala258Ser variant in the donor predicted lower incidence of severe rejection (odds ratio=0.3; 95% confidence interval, 0.1-0.9; P=0.024) and of graft loss (hazard ratio=0.5; 95% confidence interval, 0.2-1.0; P=0.046) independently of clinical risk factors. Ficolin-2 messenger RNA expression was detected in pretransplantation biopsies from 69 donor grafts. Serum and tissue ficolin-2 levels were unaffected by genotype. Ficolin-2 protein, which bound to dying cells, was detected in donor kidneys in a passenger leukocyte-like pattern. Indeed, monocytes, monocyte-derived macrophages, and peripheral blood mononuclear cells expressed ficolin-2. Donor grafts with the ficolin-2 Ala258Ser variant contained significantly elevated expression of interleukin 6, having ascribed cytoprotective effects. It has been described that Ala258Ser leads to increased binding capacity of ficolin-2 to N-acetylglucosamine.'] |
['Dihydrofolate reductase (DHFR) is a key protein involved in tetrahydrobiopterin (BH4) regeneration from 7,8-dihydrobiopterin (BH2). Dysfunctional DHFR may induce endothelial nitric oxide (NO) synthase (eNOS) uncoupling resulting in enzyme production of superoxide anions instead of NO. The mechanism by which DHFR is regulated is unknown. Here, we investigate whether eNOS-derived NO maintains DHFR stability.', 'DHFR activity, BH4 content, eNOS activity, and S-nitrosylation were assessed in human umbilical vein endothelial cells and in aortas isolated from wild-type and eNOS knockout mice. In human umbilical vein endothelial cells, depletion of intracellular NO by transfection with eNOS-specific siRNA or by the NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (PTIO)-both of which had no effect on DHFR mRNA levels-markedly reduced DHFR protein levels in parallel with increased DHFR polyubiquitination. Supplementation of S-nitroso-l-glutathione (GSNO), a NO donor, or MG132, a potent inhibitor of the 26S proteasome, prevented eNOS silencing and PTIO-induced DHFR reduction in human umbilical vein endothelial cells. PTIO suppressed S-nitrosylation of DHFR, whereas GSNO promoted DHFR S-nitrosylation. Mutational analysis confirmed that cysteine 7 of DHFR was S-nitrosylated. Cysteine 7 S-nitrosylation stabilized DHFR from ubiquitination and degradation. Experiments performed in aortas confirmed that PTIO or eNOS deficiency reduces endothelial DHFR, which can be abolished by MG132 supplementation.'] |
['Over 100\xa0million people worldwide are affected by alcohol use disorders. These conditions usually take years to develop where an initial, voluntary consumption is gradually replaced by a compulsive intake of alcohol. The exact mechanisms behind this transition remain unknown. However, ethanol (EtOH) is known to interact with several neurotransmitters and receptors in the central nervous system, and chronic EtOH consumption causes alterations in these neurotransmitter systems, proposed to contribute to the development of dependence. This study aimed to repeat previous findings that animals after long-term voluntary EtOH consumption spontaneously increase their intake. That the initial encounter with EtOH causes an elevation of dopamine in the nucleus accumbens (nAc), inducing feelings of well-being and creating an incentive to continue the behavior, has been repeatedly reported in both animals and humans. The effects of chronic EtOH consumption on this region are not as well investigated.', 'We examined both long-term EtOH consumption behavior and its consequences on expression of neurotransmitter-related genes in the nAc of the Wistar rat using quantitative polymerase chain reaction.', 'In general, the EtOH consumption of the animals in this study was modest with an average intake of 0.9\xa0g/kg/d, and only 1 of the 24 rats consuming EtOH for 10\xa0months drastically increased its intake in line with the results of Wolffgramm and Heyne (1995). Expression of the genes for dopamine receptor 2, μ-opioid receptor, and somatostatin receptor 4 were down-regulated in animals after 2 and/or 4, but not 10, months of EtOH consumption.'] |
['Several new irreversible hydrocolloid formulations have recently become available with claims of an improved dimensional stability by the manufacturers. The aim of this study was to evaluate the accuracy of casts made from alginate impression materials poured immediately and after specific storage periods.', 'Five alginates were tested: CA 37 (Cavex); Jeltrate (Dentsply Caulk); Jeltrate Plus (Dentsply Latin America); Hydrogum 5 (Zhermack); and Alginoplast (Heraeus Kulzer). A master model was mounted on a special device and used to obtain the impressions. These impressions were stored at 23 degrees C and 100% relative humidity, then poured with gypsum immediately, and again after 24, 72 and 120 hours. The casts were measured and the data were analyzed by one way analysis of variance (ANOVA) and Tukey test at p<0.05.', 'The dimensional stability of the alginate impressions was both material and time dependent (p<0.05). After 24 hours of storage, only Alginoplast and Hydrogum 5 comply with the master model (p>0.05). After 72 and 120 hours, only Hydrogum 5 was dimensionally stable (p>0.05).'] |
['Atherothrombosis is associated with platelet hyperactivity. Hypertriglyceridemia and insulin resistance (IR) are features of polycystic ovary syndrome (PCOS). The effect of induced hypertriglyceridemia on IR and platelet function was examined in young women with PCOS.', 'Following overnight fasting, 13 PCOS and 12 healthy women were infused with saline or 20% intralipid for 5 hours on separate days. Insulin sensitivity was measured using a hyperinsulinemic euglycaemic clamp in the final 2 hours of each infusion. Platelet responses to adenosine diphosphate (ADP) and prostacyclin (PGI2) were measured by flow cytometric analysis of platelet fibrinogen binding and P-selectin expression using whole blood taken during each infusion (at 2 hours) and at the end of each clamp. Lipid infusion increased triglycerides and reduced insulin sensitivity in both controls (median, interquartile range ) (5.25 [3.3, 6.48] versus 2.60 [0.88, 3.88] mg kg(-1) min(-1), P<0.001) and PCOS (3.15 [2.94, 3.85] versus 1.06 [0.72, 1.43] mg kg(-1) min(-1), P<0.001). Platelet activation by ADP was enhanced and ability to suppress platelet activation by PGI2 diminished during lipid infusion in both groups when compared to saline. Importantly, insulin infusion decreased lipid-induced platelet hyperactivity by decreasing their response to 1 μmol/L ADP (78.7% [67.9, 82.3] versus 62.8% [51.8, 73.3], P=0.02) and increasing sensitivity to 0.01 μmol/L PGI2 (67.6% [39.5, 83.8] versus 40.9% [23.8, 60.9], P=0.01) in controls, but not in PCOS.'] |
['Increased circulating endothelial progenitor cells (EPC) have been associated with a low cardiovascular risk and may be involved in endothelial cell regeneration. The present study was designed to evaluate the prognostic value of EPC in acute ischemic stroke.', 'Forty-eight patients with a first-ever nonlacunar ischemic stroke were prospectively included in the study within 12 hours of symptoms onset. Stroke severity was evaluated by the National Institutes of Health Stroke Scale, and functional outcome was assessed at 3 months by the modified Rankin Scale (mRS). Infarct volume growth between admission and days 4 to 7 was measured on multiparametric MRI. EPC colonies were defined as early outgrowth colony-forming unit-endothelial cell (CFU-EC). The increment of CFU-EC was quantified during the first week and defined as the absolute difference between the number of CFU-EC at day 7 and admission. The influence of CFU-EC increase on good functional outcome (mRS <or=2) and infarct growth was analyzed by logistic regression and linear models.', 'Patients with good outcome (n=25) showed a higher CFU-EC increment during the first week (median [quartiles], 23 [11, 36] versus -3 [-7, 1], P<0.0001) compared with patients with poor outcome. CFU-EC increment >or=4 during the first week was associated with good functional outcome at 3 months (odds ratio, 30.7; 95% CI, 2.4 to 375.7; P=0.004) after adjustment for baseline stroke severity, ischemic volume and thrombolytic treatment. For each unit increase in the CFU-EC the mean reduction in the growth of infarct volume was 0.39 (0.03 to 0.76) mL (P=0.033).'] |
['Attention-deficit/hyperactivity disorder (ADHD) and substance use disorders (SUDs) are highly comorbid and may share a genetic vulnerability. Methylphenidate (MPH), a dopamine transporter (DAT) blocker, is an effective drug for most ADHD patients. Although dopamine D4 receptor (DRD4) and dopamine transporter (DAT1) genes have a role in both disorders, little is known about how these genes influence brain response to MPH in individuals with ADHD/SUDs. The goal of this study was to evaluate whether ADHD risk alleles at DRD4 and DAT1 genes could predict the change in striatal DAT occupancy after treatment with MPH in adolescents with ADHD/SUDs.', "Seventeen adolescents with ADHD/SUDs underwent a SPECT scan with [Tc(99m) ]TRODAT-1 at baseline and after three weeks on MPH. Caudate and putamen DAT binding potential was calculated. Comparisons on DAT changes were made according to the subjects' genotype.", 'The combination of both DRD4 7-repeat allele (7R) and homozygosity for the DAT1 10-repeat allele (10/10) was significantly associated with a reduced DAT change after MPH treatment in right and left caudate and putamen, even adjusting the results for potential confounders (P ≤ 0.02; R² from 0.50 to 0.56).'] |
['We examined the effect of purified immunoglobulins G (IgG) from patients with amyotrophic lateral sclerosis (ALS) on the mobility and exocytotic release from Lysotracker-stained vesicles in cultured rat astrocytes.', 'Time-lapse confocal images were acquired, and vesicle mobility was analysed before and after the application of ALS IgG. The vesicle counts were obtained to assess cargo exocytosis from stained organelles.', 'At rest, when mobility was monitored for 2 min in bath with Ca(2+), two vesicle populations were discovered: (1) non-mobile vesicles (6.1%) with total track length (TL) < 1 μm, averaging at 0.33 ± 0.01 μm (n = 1305) and (2) mobile vesicles (93.9%) with TL > 1 μm, averaging at 3.03 ± 0.01 μm (n = 20,200). ALS IgG (0.1 mg mL(-1)) from 12 of 13 patients increased the TL of mobile vesicles by approx. 24% and maximal displacement (MD) by approx. 26% within 4 min, while the IgG from control group did not alter the vesicle mobility. The mobility enhancement by ALS IgG was reduced in extracellular solution devoid of Ca(2+), indicating that ALS IgG vesicle mobility enhancement involves changes in Ca(2+) homeostasis. To examine whether enhanced mobility relates to elevated Ca(2+) activity, cells were stimulated by 1 mm ATP, a cytosolic Ca(2+) increasing agent, in the presence (2 mm) and in the absence of extracellular Ca(2+). ATP stimulation triggered an increase in TL by approx. 7% and 12% and a decrease in MD by approx. 11% and 1%, within 4 min respectively. Interestingly, none of the stimuli triggered the release of vesicle cargo.'] |
['Cardiac arrhythmias and respiratory disturbances have been proposed as likely causes for sudden unexpected death in epilepsy. Oxygen desaturation occurs in one-third of patients with localization-related epilepsy (LRE) undergoing inpatient video-electroencephalography (EEG) telemetry (VET) as part of their presurgical workup. Ictal-related oxygen desaturation is accompanied by hypercapnia. Both abnormal lengthening and shortening of the corrected QT interval (QTc) on electrocardiography (ECG) have been reported with seizures. QTc abnormalities are associated with increased risk of sudden cardiac death. We hypothesized that there may be an association between ictal hypoxemia and cardiac repolarization abnormalities.', 'VET data from patients with refractory LRE were analyzed. Consecutive patients having at least one seizure with accompanying oxygen desaturation below 90% and artifact-free ECG data were selected. ECG during the 1 min prior to seizure onset (PRE) and during the ictal/postictal period with accompanying oxygen desaturation below 90% (DESAT) was analyzed. Consecutive QT and RR intervals were measured. In the same patients, DESAT seizures were compared with seizures without accompanying oxygen desaturation below 90% (NODESAT). For NODESAT seizures, QT and RR intervals for 2 min after seizure onset were measured.', 'Thirty-seven DESAT seizures were analyzed in 17 patients with localization-related epilepsy. A total of 2,448 QT and RR intervals were analyzed during PRE. During DESAT, 1,554 QT and RR intervals were analyzed. Twelve of the 17 patients had at least one NODESAT seizure. A total of 19 NODESAT seizures were analyzed, including 1,558 QT and RR intervals during PRE and 3,408 QT and RR intervals during NODESAT. The odds ratio for an abnormally prolonged (>457 ms) QTcH (Hodges correction method) during DESAT relative to PRE was 10.64 (p < 0.0001). The odds ratio for an abnormally shortened (<372 ms) QTcH during DESAT relative to PRE was 1.65 (p < 0.0001). Seizure-related shortening and prolongation of QTc during DESAT were also observed when Fridericia correction of the QT was applied. During DESAT seizures, the mean range of QT values (QTr) (61.14 ms) was significantly different from that during PRE (44.43 ms) (p = 0.01). There was a significant association between DESAT QTr and oxygen saturation nadir (p = 0.025) and between DESAT QTr and duration of oxygen desaturation (p < 0.0001). Both QTcH prolongation and shortening also occurred with NODESAT seizures. A seizure-associated prolonged QTcH was more likely during DESAT than NODESAT, with an odds ratio of 4.30 (p < 0.0001). A seizure-associated shortened QTcH was more likely during DESAT than NODESAT with an odds ratio of 2.13 (p < 0.0001).'] |
['Auditory neural myelination (ANM) as evaluated by auditory brainstem evoked response (ABR) during the neonatal period has been used as a surrogate outcome for long-term neurodevelopment. The validity of ANM as a surrogate outcome for long-term neurodevelopment has not been well studied.', 'Evaluate the association of ABR I-V interpeak latency (IPL), an index of ANM, at 35 week postmenstrual age (PMA) with language outcome at 3 years of age.', 'Prospective study.', '24-33 week gestational age (GA) infants were eligible if they did not meet exclusion criteria: craniofacial malformation, chromosomal disorders, deafness, auditory dys-synchrony, TORCH infection, or non-English speaking parents. Infants with malignancy, head injury, encephalopathy, meningitis, blindness, or who died or relocated were also excluded.', 'ABRs were performed at 35 week PMA using 80 dB nHL and I-V IPL (ms) measured. Auditory Comprehension (AC) and Expressive Communication (EC) were evaluated by a speech-language pathologist at 3 years of age using Preschool Language Scale.', 'Eighty infants were studied. The mean GA and birth weight of infants were 29.2 weeks and 1336 g, respectively. There was association of worse ear I-V IPL and better ear I-V IPL with AC (Coefficient-5.4, 95% CI: -9.8 to -0.9 and Coefficient-5.5, 95% CI: -10 to-0.9, respectively) and EC (Coefficient-5.6, 95% CI: -9.5 to-1.8 and Coefficient-6.7, 95% CI: -10.6 to-2.7, respectively) after controlling for confounders.'] |
['We examined whether patients with a diagnosis of fibromyalgia have an increased risk of coronary heart disease (CHD), compared with age- and sex-matched control patients. We hypothesized that patients diagnosed with fibromyalgia are at increased risk of adverse coronary events.', 'Using a matched-cohort study design, we analyzed data retrieved from the Longitudinal Health Insurance Database 2000 released by the National Health Research Institute, Taiwan. The Longitudinal Health Insurance Database 2000 includes medical claims data and registration files for 1 million enrollees randomly selected from the 2000 Registry for Beneficiaries (n = 23.72 million) of the National Health Insurance program. Patients treated for fibromyalgia at least once a month for 3 consecutive months following their initial diagnosis were enrolled in our study. The primary end point was the composite of CHD events, including percutaneous coronary interventions and coronary artery bypass grafting procedures. A propensity score was estimated by a logistic regression method, in which the fibromyalgia status was regressed on baseline prognostic factors. The hazard ratios and the 95% confidence intervals were estimated using multivariate Cox proportional-hazards regression models while adjusting for the propensity score.', 'After adjusting for the propensity score, the patients with fibromyalgia showed a significantly higher subsequent risk of a CHD event (hazard ratio, 2.11; 95% confidence interval, 1.46-3.05; P < 0.001) than the patients without fibromyalgia.'] |
['The tumor suppressor p53 plays a key role in regulating the cell cycle and apoptosis in differentiated cells. Mutant mice lacking functional p53 develop normally but die from multiple neoplasms shortly after birth. There have been hints that p53 is involved in morphogenesis, but given the relatively normal development of p53 null mice, the significance of these data has been difficult to evaluate. To examine the role of p53 in vertebrate development, we have determined the results of blocking its activity in embryos of the frog Xenopus laevis.', 'Two different methods have been used to block p53 protein activity in developing Xenopus embryos--ectopic expression of dominant-negative forms of human p53 and ectopic expression of the p53 negative regulator, Xenopus dm-2. In both instances, inhibition of p53 activity blocked the ability of Xenopus early blastomeres to undergo differentiation and resulted in the formation of large cellular masses reminiscent of tumors. The ability of mutant p53 to induce such developmental tumors was suppressed by co-injection with wild-type human or wild-type Xenopus p53. Cells expressing mutant p53 activated zygotic gene expression and underwent the mid-blastula transition normally. Such cells continued to divide at approximately normal rates but did not form normal embryonic tissues and never underwent terminal differentiation, remaining as large, yolk-filled cell masses that were often associated with the neural tube or epidermis.'] |
['The advantages of simultaneous bilateral procedures in joint arthroplasty have been widely described for in total joint replacements of both the hip and the knee. In contrast, unicompartmental knee arthroplasties, despite their effectiveness in pain relieving and functional improvement, are underinvestigated in these terms. The purpose of this study is to assess the possible benefits and risks of bilateral simultaneous knee replacements, in comparison with unilateral procedures.', 'A total of 567 surgery reports of bilateral simultaneous (220) or unilateral (347) unicompartmental knee arthroplasties were analysed to collect study parameters. Information like the onset of complications and need for revisions were recorded by phone interview (at least two years after surgery). All surgeries were performed by the same orthopaedic surgeon, assisted by the same anesthesiologist.', 'Complication and revision rates, as well as the length of hospital stay were similar between the two study groups, while blood and haemoglobin losses, and consequently the use of transfusion of allogeneic and autologous blood units, were higher in the simultaneous bilateral group.'] |
["Fluorescent dyes, used frequently to label proteins for microvascular experiments, are assumed to not alter the protein's physicochemical characteristics. We tested the validity of that assumption for two probes, bovine serum albumin (BSA) and alpha-lactalbumin.", 'Standard electrophoretic techniques were used to examine the influence of five fluorescent dyes on the following three properties of BSA: molecular size (sodium dodecyl sulfate-polyacrylamide gel electrophoresis [PAGE]); relative molecular charge (native PAGE); and isoelectric point (pI) (i.e., isoelectric focusing). Also examined were the influence of the dyes on the relative charge of alpha-lactalbumin (native PAGE). Paired measures of single-vessel flux were made using two commercial preparations of dye-BSA on porcine coronary arterioles and venules.', 'The addition of fluorescein isothiocyanate (FITC) to BSA altered significantly its size (p < 0.01; n = 6), relative charge (p < 0.02; n = 7), and pI. The other dyes caused minimal, yet significant, changes on the relative charge of BSA without influencing size or pI. Only FITC altered the relative charge of alpha-lactalbumin. While arteriolar fluxes of FITC-BSA and tetramethyl rhodamine isothiocyanate (TRITC)-BSA did not differ (p = 0.43; n = 5), in venules the FITC-BSA flux was greater than the TRITC-BSA flux (p < 0.001; n = 6).'] |
['A blockade of CD44 is considered a therapeutic option for the elimination of leukemia initiating cells. However, anti-panCD44 can interfere with hematopoiesis. Therefore we explored, whether a CD44 variant isoform (CD44v)-specific antibody can inhibit leukemia growth without attacking hematopoiesis. As a model we used CD44v10 transfected EL4 thymoma cells (EL4-v10).', 'The therapeutic efficacy of anti-panCD44 and anti-CD44v10 was evaluated after intravenous application of EL4/EL4-v10. Ex vivo and in vitro studies evaluated the impact of anti-panCD44 and anti-CD44v10 as well as of EL4 and EL4-v10 on hematopoietic stem cells (HSC) in cocultures with bone marrow stroma cells with a focus on adhesion, migration, cell cycle progression and apoptosis resistance.', 'Intravenously injected EL4-v10 grow in bone marrow and spleen. Anti-panCD44 and, more pronounced anti-CD44v10 prolong the survival time. The higher efficacy of anti-CD44v10 compared to anti-panCD44 does not rely on stronger antibody-dependent cellular cytotoxicity or on promoting EL4-v10 apoptosis. Instead, EL4 compete with HSC niche embedding. This has consequences on quiescence and apoptosis-protecting signals provided by the stroma. Anti-panCD44, too, more efficiently affected embedding of HSC than of EL4 in the bone marrow stroma. EL4-v10, by catching osteopontin, migrated on bone marrow stroma and did not or weakly interfere with HSC adhesion. Anti-CD44v10, too, did not affect the HSC--bone marrow stroma crosstalk.'] |
['No previous study has examined the comorbidity of Irritable Bowel Syndrome (IBS) and Generalized Anxiety Disorder (GAD) in a general population using standardized diagnostic methods.', 'To examine the prevalence, comorbidity and risk correlates of IBS and GAD in a general population.', 'A random community-based telephone survey was conducted. The questionnaire covered symptoms of IBS, GAD, core depressive symptoms, help-seeking behaviour and functional impairment on the Sheehan Disability Scale.', 'A total of 2005 participants completed the interview. The current prevalence of IBS was 5.4% and the 12-month prevalence of GAD was 4%. GAD was five times more common among IBS respondents than non-IBS respondents (OR: 5.84, P < 0.001), whereas IBS was 4.7 times more common among GAD respondents than among non-GAD respondents (OR: 6.32, P < 0.001). Core depressive symptoms (OR: 6.25, P < 0.01) and education level (OR: 5.918, P = 0.021) were risk correlates of GAD among IBS respondents. Comorbid respondents were more impaired than respondents having either disorder alone, but were not more likely to seek professional help than IBS-only respondents.'] |
['Since hyperglycemia-induced cellular dysfunction could be associated with alterations of the immune system, we tested the hypothesis that hyperglycemia augments the aberrant immune responses such as inflammation and differentiation of CD4(+) T lymphocytes in the mesenteric lymph nodes (MLNs), and induces alterations of microbiota both under physiological and pathological conditions.', 'Male Wistar rats were randomly allocated into 4 groups: Control and Endotoxemia (lipopolysaccharide, LPS 1\xa0mg/kg) with or without hyperglycemia. The hyperglycemia groups were administered glucose solution (10-40\xa0%), while the normoglycemia groups were administered saline. Alterations of the mRNA expressions of inflammatory cytokines and CD4(+) T lymphocyte transcriptional factor expressions in the MLNs, and those of the intestinal microbiota were analyzed at 24\xa0hr.', 'Hyperglycemia was kept approximately 250-350\xa0mg/dL during the 24\xa0hr study period. At the end of 24\xa0hr, hyperglycemia augmented the mRNA expressions of interleukin (IL)-1β and IL-6 in the MLNs, while both the helper T (Th) 2 and regulatory-T (Treg) transcriptional factors were simultaneously up-regulated under non-endotoxemic condition. LPS injection significantly modulated the obligate anaerobe bacterial populations of the Bacteroidetes class, and altered the population sizes of the Clostridium perfringens and the Bacteroides fragilis subgroup. Hyperglycemia did not enhance these alterations of the microbiota evoked by LPS, although it did modify the bacterial populations of the L. reuteri subgroup and staphylococci in healthy condition without endotoxemia.'] |
['To find out if erythromycin (a motilin agonist) accelerated gastric emptying after vagotomy and in normal subjects.', 'Double blind controlled study.', 'Two referral centres.', '15 patients who had previously undergone vagotomy and who did (n = 8) or did not (n = 7) have symptoms of gastric stasis and 10 normal controls.', 'A standard meal containing 185 x 10(5) Bq -99mTc was eaten after either erythromycin 200 mg or 40 ml placebo (normal saline) had been given intravenously. Subjects were then scanned by gamma camera.', 'Measurement of: the length of time from completion of the meal to the onset of gastric emptying; the length of time from completion of the meal until half of the meal had left the stomach; the length of the time from the onset of gastric emptying until half of the meal had left the stomach; and the percentage of the meal that was left in the stomach at 60 and 120 min after the end of the meal.', 'Gastric emptying was significantly delayed in those patients with symptoms compared with normal subjects and patients without symptoms. Erythromycin accelerated the first two phases of gastric emptying in all patients and normal subjects, but did not affect the length of time from the onset of gastric emptying until half the meal had left the stomach.'] |
['Increased levels of homocysteine (Hcy) form an independent risk factor for cardiovascular disease. In a previous study we have shown that Hcy induced phosphatidylserine (PS) exposure to the outer leaflet of the plasma membrane in cardiomyocytes, inducing a pro-inflammatory phenotype. In the present study the mechanism(s) involved in Hcy-induced PS exposure were analyzed.', 'H9c2 rat cardiomyoblasts were subjected to 2.5 mM D,L-Hcy and analyzed for RhoA translocation and activity, Rho Kinase (ROCK) activity and expression and flippase activity. In addition, the effect of ROCK inhibition with Y27632 on Hcy-induced PS exposure and flippase activity was analyzed. Furthermore, GTP and ATP levels were determined.', 'Incubation of H9c2 cells with 2.5 mM D,L-Hcy did not inhibit RhoA translocation to the plasma membrane. Neither did it inhibit activation of RhoA, even though GTP levels were significantly decreased. Hcy did significantly inhibit ROCK activation, but not its expression, and did inhibit flippase activity, in advance of a significant decrease in ATP levels. ROCK inhibition via Y27632 did not have significant added effects on this.'] |
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