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['The heme oxygenase-1 (HO-1) system is associated with the rate-limiting step of conversion of heme, one of the most critical roles in cytoprotective mechanisms. Our study investigated its potential role in protection of endothelial cells from T cells.', 'The recombinant plasmid pcDNA3-HO-1 was transfected into endothelial cells. Indirect fluorescent staining was used to examine the expression of HO-1 protein. Then endothelial cells primed by INF-gamma were mixed in culture with Jurkat T cells labeled with carboxyfluorescein diacetate succinimidyl ester (CFSE). The number of adhesive Jurkat T cells was determined using FACS to evaluate the adhesion effect. After being cultured with endothelial cells, the cell cycle of Jurkat T cells was detected using FACS.', 'Expression of HO-1 on endothelial cells conferred significant protection against Jurkat T-cell-mediated adhesion. The rate of Jurkat T-cell adhesions was reduced to 19.06%, in contrast with 31.42% in the control group (P<.05). After using ZnPP, an inhibitor of HO-1, the rate of Jurkat T-cell adhesion recovered to 29.08%. The binding activities between endothelial cells and Jurkat T cells was blocked by HO-1 expression. The proliferation of Jurkat T cells was inhibited after culture with endothelial cells, which had been transfected with HO-1, which blocked cell cycle entry of T cells. More than 60% of Jurkat T cells remained in G0/G1 compared with 40% among the control group.']

['Montreal Cognitive Assessment (MoCA) has been proposed as a screening tool in vascular cognitive impairment. Diffusion tensor imaging is sensitive to white matter microstructural damage. We investigated if diffusion tensor imaging-derived indices are more strongly associated with performances on MoCA or on the widely used mini mental state examination in patients with mild cognitive impairment and small vessel disease.', 'Mild cognitive impairment patients with moderate/severe degrees of white matter hyperintensities on MRI were enrolled. Lacunar infarcts, cortical atrophy, medial temporal lobe atrophy and median values of mean diffusivity and fractional anisotropy of the cerebral white matter were studied and correlated with cognitive tests performances.', 'Seventy-six patients (mean age 75.1±6.8 years, mean years of education 8.0±4.3) were assessed. In univariate analyses, a significant association of both MoCA and mini mental state examination scores with age, education, cortical atrophy, and medial temporal lobe atrophy was found, whereas mean diffusivity and fractional anisotropy were associated with MoCA. In partial correlation analyses, adjusting for all demographic and neuroimaging variables, both mean diffusivity and fractional anisotropy were associated only with MoCA (mean diffusivity: r= -0.275, P=0.023; fractional anisotropy: r=0.246, P=0.043).']

['Anticytomegalovirus (CMV) prophylaxis prevents the acute disease but its impact on subclinical infection and allograft outcome is unknown. We sought to determine whether CMV prophylaxis administered for three months after heart transplant would improve patient outcomes.', 'This prospective cohort study of 66 heart transplant recipients compared aggressive CMV prophylaxis (n = 21, CMV hyperimmune globulin [CMVIG] plus four weeks of intravenous ganciclovir followed by two months of valganciclovir); with standard prophylaxis (n = 45, intravenous ganciclovir for four weeks). Prophylaxis was based on pretransplant donor (D) and recipient (R) CMV serology: R-/D+ received aggressive prophylaxis; R+ received standard prophylaxis. Outcome measures were: CMV infection assessed by DNA-polymerase chain reaction on peripheral blood polymorphonuclear leukocytes, acute rejection, and cardiac allograft vascular disease (CAV) assessed by intravascular ultrasound. All patients completed one year of follow-up. RESULTS.: CMV infection was subclinical in all but four patients (two in each group). Aggressively treated patients had a lower incidence of CMV infection (73 +/- 10% vs. 94 +/- 4%; P = 0.038), and an independent reduced relative risk for acute rejection graded > or =3A (relative risk [95% CI] = 0.55 [0.26-0.96]; P = 0.03), as compared with the standard prophylaxis group. Aggressively prophylaxed patients also showed a slower progression of CAV, in terms of coronary artery lumen loss (lumen volume change=-21 +/- 13% vs. -10+/-14%; P = 0.05); and vessel shrinkage (vessel volume change = -15 +/- 11% vs. -3 +/- 18%; P = 0.03).']

['The objective of this study is to evaluate the feasibility of using coated microneedles to deliver vaccines into the oral cavity to induce systemic and mucosal immune responses.', 'Microneedles were coated with sulforhodamine, ovalbumin and two HIV antigens. Coated microneedles were inserted into the inner lower lip and dorsal surface of the tongue of rabbits. Histology was used to confirm microneedle insertion, and systemic and mucosal immune responses were characterized by measuring antigen-specific immunoglobulin G (IgG) in serum and immunoglobulin A (IgA) in saliva, respectively.', 'Histological evaluation of tissues shows that coated microneedles can penetrate the lip and tongue to deliver coatings. Using ovalbumin as a model antigen it was found that the lip and the tongue are equally immunogenic sites for vaccination. Importantly, both sites also induced a significant (p\u2009<\u20090.05) secretory IgA in saliva compared to pre-immune saliva. Microneedle-based oral cavity vaccination was also compared to the intramuscular route using two HIV antigens, a virus-like particle and a DNA vaccine. Microneedle-based delivery to the oral cavity and the intramuscular route exhibited similar (p\u2009>\u20090.05) yet significant (p\u2009<\u20090.05) levels of antigen-specific IgG in serum. However, only the microneedle-based oral cavity vaccination group stimulated a significantly higher (p\u2009<\u20090.05) antigen-specific IgA response in saliva, but not intramuscular injection.']

['Traditional Chinese medicine herbs (TCMHs) are used in medicines as well as in daily dietary supplements in Asia. In this study, we employed pNF-kappaB-Luc or pIFN-gamma-Luc and BALB/c mice peritoneal macrophages or splenocytes to investigate both the immune and inflammatory effects of six selected plant species.', 'Specifically, we used ethyl acetate fractions of Astragalus membranaceus (Fisch.) Bunge var. mongholicus (Bunge) Hsiao (Fabaceae) (AM), Andrographis paniculata (Burm. f.) Nees (Acanthaceae) (AP), Angelica sinensis (Oliv.) Diels (Apiaceae) (AS), Eucommia ulmodes Oliv. (Eucommiaceae) leaves (EU leaves), Isatis indigotica Fort. (Brassicaceae) (II) and Morus alba L. (Moraceae) (MA).', 'We found that ethyl acetate fractions of AP, AS and MA significantly decreased NF-kappaB luciferase activity and also the secretion of NO and PGE(2) in LPS/IFN-gamma stimulated mouse peritoneal macrophages (p<0.05). In contrast, they did not affect IFN-gamma luciferase activity or IFN-gamma production in concanavalin A (Con A)-activated mouse splenocytes. Our results indicated that the anti-inflammatory properties of these plant extracts might be resulted from the inhibition of pro-inflammatory mediators (e.g., NO and PGE(2)), at least in part via suppression of a signaling pathway such as NF-kappaB.']

['To investigate the pattern of presentation of cervical cancer and to identify the characteristics of women who present symptomatically with cervical cancer.', 'A retrospective study of all cervical cancer cases diagnosed over a 4-year period. Details of mode of presentation, stage at diagnosis and cytological/gynaecological history were collated.', 'In total, 148 cases were identified with a median age of 46 years (range, 20-91 years). In this population, 112 (75.7%) women were within the screening age range. Forty-eight (33.6%) were asymptomatic at diagnosis and presented through the colposcopy clinic. All asymptomatic women (100%) had stage I disease at diagnosis, compared with 37.2% of the symptomatic group (P < 0.001). Postmenopausal bleeding was the most common presenting symptom (33%), followed by postcoital bleeding (14.2%), intermenstrual bleeding (12.2%) and increased vaginal discharge (3.4%). The majority of symptomatic women presented through colposcopy, gynaecological oncology or gynaecology clinics (87.6%); however, 6.5% presented through the emergency department. Women who presented symptomatically were significantly older than asymptomatic women (54.9 versus 38.1 years, P < 0.001). Women at risk of social isolation (non-English speakers, alcohol abusers, heavy smokers, receiving treatment for psychiatric disease) were more likely to present with symptoms, through the emergency department and with advanced disease at diagnosis (stage II+) (P < 0.001).']

['Many smokers report smoking because it helps them modulate their negative affect (NA). The stress induction model of smoking suggests, however, that smoking causes stress and concomitant NA. Empirical support for the stress induction model has primarily derived from retrospective reports and experimental manipulations with non-representative samples of smokers. Moreover, prior studies have typically not considered contextual factors (e.g., daily stressors) that may impact the smoking-NA relationship.', 'The aim of this study was to assess the stress induction model of smoking using a prospective design in a nationally representative sample of smokers while simultaneously examining the impact of daily stressors on the relationship between smoking and NA. We hypothesized that smoking and NA would be positively related, and this relationship would be intensified by exposure to daily stressors.', 'A national sample of middle-aged smokers (N = 256) were called on eight consecutive evenings to assess stressor exposure and intensity. Participants also reported on their daily NA and indicated the number of cigarettes they smoked. Analyses were conducted using hierarchical linear modeling to determine the relationship between daily smoking, NA, and stress.', 'Smoking more than usual was associated with increased NA on days when respondents were exposed to any stressors. Smoking more than usual had no effect on NA on days when no stressors were encountered. Moreover, the moderating effect of stressor exposure remained significant even after controlling for the number and intensity of daily stressors reported.']

['Copper toxicosis (CT) in Bedlington terriers is an autosomal recessive disorder characterized by massive lysosomal copper accumulation in livers of affected dogs, and a defect in the biliary excretion of this metal. We propose that MURR1, the gene defective in canine CT, has a role in the regulation of copper excretion into bile during copper overload.', 'Polyclonal antibodies raised against full-length recombinant human MURR1 were used for immunoblot analysis and indirect immunofluorescence studies.', 'Using Western blot analysis, these antibodies abundantly detected MURR1 as a 23 kDa protein in liver extracts of mice and dogs, but MURR1 was undetectable in the livers of affected Bedlington terriers. MURR1 was also detected in different tissues and cell lines; in cell lines the protein was found both in cytosol and membrane preparations. Consistent with this observation, indirect immunofluorescence staining revealed that in some cells MURR1 was associated with a vesicular compartment diffusely localized throughout the cell.']

['To assess if predefined variables in study design, instrument type, and patient characteristics account for variance in reported retest reliability for the Oswestry Disability Index (ODI) and Roland-Morris Questionnaire (RMQ). A second aim was a more precise estimate of instrument reliability.', 'A systematic literature search of MEDLINE, EMBASE, AMED, PsycINFO, and CINAHL was performed from inception to January 2011. Hand search, gray literature, and reference retrieval completed the search. Two blinded reviewers extracted the data. Original authors were contacted for the missing data. A meta-analysis was performed with the intraclass correlation coefficient as the outcome measure.', 'Fifty studies on 31 ODI and 28 RMQ cohorts were retrieved that met the inclusion criteria. Meta-analysis found the ODI more reliable than the RMQ (coefficient, -0.2840; P = 0.009) and lower reliability on increased days to retest (coefficient, -0.0089; P = 0.005) and in low back pain (LBP) with leg pain than LBP only cohorts (coefficient, -0.2194; P = 0.046). The use of a transition item to identify stable patients and percentage of cohort not included at retest were significant only on single variable analysis.']

['A reclassification of the International Union Against Cancer (UICC) staging system for adrenocortical carcinoma (ACC) patients has recently been proposed by the European Network for the Study of Adrenal Tumors (ENSAT) to better discriminate between cancer-specific mortality (CSM) risk strata. We formally tested the validity of the modified staging system in a large North American population-based cohort.', "Kaplan-Meier survival curves depicted CSM rates in the overall population and after stratification according to the 2004 UICC or the 2008 ENSAT-staging system. Cox regression models addressing CSM tested the prognostic value of respectively the UICC or the ENSAT-staging system. Harrell's concordance index quantified the accuracy of the standard versus the modified staging system.", 'In the overall population (n=573), the CSM-free survival rates at 1, 3, and 5 years were, respectively, 62.9%, 47.0%, and 38.1%. No statistically significant differences in survival were recorded between 2004 UICC stages II and III patients (p=0.1). Conversely, a statistically significant difference was observed between 2008 ENSAT stage II and stage III patients (p<0.001). The 2008 ENSAT-staging system showed higher accuracy (83.0%) in predicting 3-year CSM rates, relative to the 2004 UICC-staging system (79.5%) (p<0.001).']

['Drug challenges in "intact" and p-chlorophenylalanine (p-CPA)-treated animals can be used to distinguish agents that act as direct serotonin (5-HT) agonists from agents that function as 5-HT releasers.', 'The objective of the study was to investigate the effect of p-CPA treatment on the capacity of racemic 3,4-methylenedioxymethamphetamine (MDMA) and its stereoisomers to induce the head twitch response, hyperthermia, and locomotor stimulation in mice.', 'Pretreatments with either 100 mg/kg p-CPA or equivolume saline were administered for three consecutive days. The following day, mice were either euthanized (to quantify 5-HT tone), tested with various doses of racemic MDMA or one of its enantiomers in the head twitch assay, or challenged with 32 mg/kg racemic MDMA or one of its enantiomers, while temperature and locomotor activity were monitored via radiotelemetry.', 'p-CPA reduced cortical 5-HT turnover by >70% without altering dopamine turnover. Racemic MDMA did not induce a significant head twitch response in intact or p-CPA-treated mice. S(+)-MDMA and R(-)-MDMA elicited similar head twitch curves in intact mice; p-CPA treatment attenuated this response when induced by S(+)-MDMA but not when elicited by R(-)-MDMA. Neither the hyperthermic nor locomotor-stimulant effects of racemic MDMA were altered by p-CPA treatment. The hyperthermic effects, but not the locomotor-stimulant effects, of S(+)-MDMA were attenuated in mice treated with p-CPA. R(-)-MDMA did not alter core temperature or induce significant locomotor stimulation in intact or p-CPA-treated mice.']

['Statins are prescribed for their preventative effects within atherosclerosis development. To our knowledge, no study focusing on very low-dose (non-hypolipidemic effect) and long-term atorvastatin treatment in\xa0vivo was available. Our aim was to assess the effect of such atorvastatin treatment on the mechanical and functional characteristics of arteries in the context of primary prevention.', 'An atorvastatin treatment (2.5\xa0mg/kg/day) was tested against controls on 34 male 3 to 12 month-old WHHL rabbits. No effect on total cholesterol, triglycerides, HDL or LDL was observed. The arterial stiffness was evaluated on vigil animals by pulse wave velocity (PWV) measurement. Then, in\xa0vitro measurements were made to evaluate (1) the endothelial and vascular smooth muscle function, (2) the elasticity of the arterial wall and (3) the composition in collagen and elastin in the aorta.', "The PWV increasing observed with age in control group was canceled by treatment, creating a significance difference between groups at 12 months (5.17\xa0±\xa00.50 vs 2.14\xa0±\xa00.34\xa0m\xa0s(-1) in control and treated groups respectively). Vasoreactivity modifications can't explain this result but maintain of elasticity with treatment in large arteries was confirm by a static tensile test. A first possible explanation is the change of wall composition with treatment, validated by the percentage of elastin at 12 months, 4.4% lower in the control group compared to the treated group (p\xa0<\xa00.05)."]

['Malignant pleural mesotheliomas (MPMs) are aggressive tumors with a poor prognosis. We aimed to clarify the mechanisms of epithelial-to-mesenchymal transition (EMT) in MPMs by analyzing the expressions of EMT-associated transcription factors and E-cadherin in relation to tumor proliferation rates and patient survival.', 'One hundred nine patients with MPMs were investigated. Among these patients, there were 61 epithelioid tumors, 21 sarcomatoid tumors, 20 biphasic tumors, and 7 desmoplastic tumors. Immunohistochemical analyses were performed to evaluate the expressions of Snail, ZEB1, Twist, E-cadherin, and the Ki-67 proliferation index.', 'The expressions of Snail and ZEB1 were significantly higher in the nonepithelioid tumors than in the epithelioid tumors (p<0.0001 and p=0.0051, respectively). Furthermore, the E-cadherin expression was significantly lower in the Snail-high tumors than in the Snail-low tumors (p=0.0423). The E-cadherin expression was significantly lower in the nonepithelioid tumors than in the epithelioid tumors (p=0.0126). The Ki-67 proliferation index was significantly higher in the nonepithelioid tumors than in the epithelioid tumors (p=0.025). Patient survival was significantly lower in patients with Snail-high MPMs than in those with Snail-low MPMs (p=0.0016), especially in patients with nonepithelioid tumors (p=0.0089). The multivariate analysis also demonstrated that nuclear Snail expression was a significant predictor of poor prognosis in patients with MPMs (p=0.0142).']

['Transplacental transfer of nutritive and inhalant allergens has been described being potentially responsible for a series of events leading to antigen-specific immune responses in the fetus. As such, cord blood T cell responses appear ubiquitously. However, studies failed to reveal a consistent dose-response relationship between antenatal allergen exposure and allergen-specific cellular reactivity in cord blood.', 'To examine the transfer process of allergens (ovalbumin (OVA), beta-lactoglobulin (BLG), birch pollen allergen Bet v1) in placental tissue (BeWo cell line, ex vivo placenta model).', 'The choriocarcinoma cell line BeWo was used to study the allergen uptake and transfer experiments in vitro. In the ex vivo placenta model the contribution of different placental compartments was evaluated. For this, immuno-histochemistry, immuno-electronmicroscopy and ELISA techniques were applied using monoclonal antibodies to Bet v1, OVA and -BLG.', 'In vitro transfer studies on a BeWo cell-layer revealed an intracellular allergen uptake and a trans-trophoblastic allergen transfer, which was temperature- and concentration dependent, pH sensitive and asymmetric. Allergen-specific staining of placental tissue after allergen perfusion (BLG) demonstrated bulk of the allergen in the syncytio-trophoblastic cell layer and minor staining in the villous stroma and in the endothelium of fetal vessels. Immunogold staining revealed an accumulation of the perfused allergen in the trophoblastic basement membrane.']

['Delirium is an organically caused acute dysfunction of the brain associated with increased morbidity, mortality, cost of care and poor cognitive recovery.', "This point prevalence study of delirium was conducted at Hvidovre Hospital, Copenhagen, Denmark at two separate occasions. Patients were examined with the Brief Confusion Assessment Method (bCAM) in both, but in the second survey bCAM was supplemented with a psychiatric assessment using the Diagnostic and Statistical Manual of Mental Disorders, fourth ed. In all, 126 patients were assessed and eight patients were excluded. The delirious patients' charts were examined.", 'Out of the 118 patients included in the study, 38 (32%) were delirious and in 18 (47%) patients, the diagnosis was documented. Furthermore, in 18 (47%) patients, a pharmacological treatment plan for agitation was prepared (in 89% of those diagnosed with delirium and in 10% of those without the diagnosis). In 26 (68%), a plan to increase care existed (in 78% of those with a diagnosis of delirium and in 60% without the diagnosis). In 11 patients (29%), there was a plan for reducing stress (in 44% of those with a diagnosis of delirium and in 15% without the diagnosis).']

['The objective of this study is to investigate the characteristics of esophageal motor activity responsible for the development of gastroesophageal reflux (GER) in patients with esophageal atresia (EA).', 'The subjects consisted of 29 patients with EA (1 month to 19 years). Computerized esophageal manometry was conducted to investigate esophageal contractions at swallow. A topographic esophageal manometric analysis was conducted in each subject, providing 3-dimensional displays to reveal the pressure continuum representing esophageal contractions.', 'Significant contractions in the middle esophagus just below the anastomosis were absent in all subjects. Contractions in the distal esophagus were conspicuously absent in 17 subjects. Of these 17, 6 had already undergone fundoplication, and 9 had symptomatic GER requiring fundoplication subsequent to this study. The remaining 12 patients had contractions in the distal esophagus and did not require medical/surgical intervention. A lack of distal esophageal contractions was significantly correlated with the development of GER (P < .001). There was a significant difference in esophageal acid exposure between the 2 groups (median, 38% vs 4%, P < .001).']

['Cardiac disease accounts for a large burden of premature mortality and morbidity in patients with type 1 myotonic dystrophy (MD). However, little is known about structural cardiac abnormalities particularly in asymptomatic patients with MD. We sought to describe the prevalence and extent of structural cardiac abnormalities in patients with MD and to assess their association with functional, electrical, biochemical and genetic disturbances.', 'In this case-control study, 40 adults with MD who had no contraindications to cardiac MRI (CMR) were identified from the Grampian region genetic database. Forty-one age-and-gender-matched healthy volunteers were also recruited. All subjects underwent detailed assessment including CMR, echocardiography, electrocardiography, signal-averaged electrocardiography, Holter monitoring and quantification of serum B-type natriuretic peptide (BNP). Genetic testing of patients with MD was performed with quantification of CTG trinucleotide repeat sequences. Results of clinical, electrical, genetic and biochemical investigations were correlated with cardiac structural and functional abnormalities detected on CMR.', 'Electrical disturbances including prolongation of PR (187±29 vs 156±23\u2005ms, p<0.001) and QRS intervals (99±11 vs 89±9\u2005ms, p<0.001) were the most prevalent abnormality. Patients with MD had a significantly lower left ventricular (LV) mass (142±44 vs 172±73\u2005g, p=0.03) and lower right ventricular (RV) ejection fraction (46±9 vs 50±7%, p=0.02) compared with controls, although LV ejection fraction was similar between the groups (58±8 vs 59±6%, p=0.34). LV non-compaction was also significantly more prevalent in the MD cohort (35% vs 12%, p=0.019). Late gadolinium enhancement was present in 13% of patients with MD. Muscular disability scores correlated with electrical changes (r=0.529, p<0.001); however, the number of CTG repeat sequences did not correlate with either electrical or structural abnormalities.']

['To study the effects of introducing an Enhanced Recovery After Surgery (ERAS) protocol, modified for gynecological surgery, on length of stay and complications following abdominal hysterectomy.', 'Observational study.', 'Department of Obstetrics and Gynecology, Örebro University Hospital, Sweden.', 'Eighty-five patients undergoing abdominal hysterectomy for benign or malignant indications between January and December 2012, with or without salpingo-oophorectomy. Outcomes were compared with all consecutive patients who had undergone the same surgery from January to December 2011, immediately before establishing the ERAS protocol (n\xa0=\xa0120).', 'The ERAS protocol was initiated in January 2012 as part of a targeted implementation program. Data were extracted from patient records and from a specific database.', 'Length of stay and the proportion of patients achieving target length of stay (2\xa0days).', 'Length of stay was significantly reduced in the study population after introducing the ERAS protocol from a mean of 2.6 (SD 1.1) days to a mean of 2.3 (SD 1.2) days (p\xa0=\xa00.011). The proportion of patients discharged at 2\xa0days was significantly increased from 56% pre-ERAS to 73% after ERAS (p\xa0=\xa00.012). No differences were found in complications (5% vs. 3.5% in primary stay, 12% vs. 15% within 30\xa0days after discharge), reoperations (2% vs. 1%) or readmission (4% vs. 4%).']

['Stentless aortic valve prostheses have excellent hemodynamic profiles, but may be associated with an increased postoperative heart block when compared to conventional prostheses.', 'To assess the effect of an alternative subcoronary implantation technique on postoperative complete heart block (CHB) and permanent pacemaker implantation (PPI) following aortic valve replacement (AVR) with stentless tissue valves.', 'A total of 130 consecutive patients undergoing AVR with stentless tissue valves by a single surgeon were studied retrospectively.', 'A stentless tissue valve was implanted into 80 patients using the conventional modified subcoronary implantation technique, and 50 patients received a stentless tissue valve by an alternative subcoronary technique in which the inflow suture line is raised at the level of right-non coronary commissure. Data were collected at the time of hospital discharge and at 6-12 months postoperatively.', 'Independent samples t-test was used to compare continuous variables, and categorical variables were compared with the chi-square test.', 'Use of this new method reduced postoperative CHB (4.0% vs. 16.3%, P = 0.033), with fewer patients requiring PPI in the early postoperative period (6.0% vs. 18.8%, P = 0.041). Echocardiographic examination showed no differences in the effective orifice area, peak and mean aortic valve gradients, or left ventricular mass index between groups. Trivial or mild aortic regurgitation was found in 3.9% of patients with the conventional modified technique and 4.0% of patients undergoing the alternative technique, during follow-up (P > 0.05).']

['To compare a new insertion method using an EndoGlide (Angiotech/Network Medical Products) with the standard Busin glide (Moria USA) assisted insertion of the posterior lamellar corneal graft in Descemet stripping endothelial keratoplasty (DSEK).', 'Prospective, consecutive, comparative, nonrandomized study.', 'Surgery was performed between October 2008 and October 2010 in 52 eyes of 52 consecutive patients with endothelial dysfunction suitable for DSEK. Twenty-two consecutive eyes underwent the new EndoGlide-assisted insertion of donor lenticule and 30 eyes underwent the surgery using the Busin glide. Six-month follow-up data are available for all patients. Clinical details, best-corrected visual acuity, manifest refraction, intraoperative and postoperative complications, and corneal endothelial cell loss were assessed at 6 months after DSEK.', 'At 6 months after surgery, the best-corrected visual acuity was similar in both groups (0.13 logarithm of the minimal angle of resolution in the EndoGlide eyes as compared with 0.15 logarithm of the minimal angle of resolution in the Busin group; P = .34). Mean spherical equivalent was 0.65 diopter (D) and 0.51 D, and mean refractory cylinder was 1.39 D and 1.08 D, respectively (P = .40). The endothelial cell loss was much lower in the EndoGlide group (25.76%) as compared with the Busin group (47.46%; P < .0001).']

['Lower-extremity injuries constitute the leading cause of trauma hospitalizations among people under the age of 65 years. Rehabilitation has the potential to favorably influence the outcomes associated with traumatic lower-extremity injuries.', 'The objectives of this study were to explore variability in surgeon and physical therapist assessments of the need for physical therapy in patients with traumatic lower-extremity injuries and to determine the factors associated with assessments of need.', 'This study was a retrospective cohort investigation.', 'Participants were 395 patients treated by reconstruction in the Lower-Extremity Assessment Project. They were evaluated at 8 level I trauma centers at 3, 6, and 12 months after hospitalization by an orthopedic surgeon and a physical therapist to determine the need for physical therapy. Analyses included multilevel logistic regression.', 'Chi-square analyses showed that surgeon and therapist assessments of need differed statistically across trauma centers. Surgeons were more likely to assess a need for therapy at 3 months when participants had low work self-efficacy, impaired knee flexion range of motion (ROM), and weight-bearing limitations and at 6 and 12 months when participants had impaired knee flexion ROM and weight-bearing and balance limitations. Therapists were more likely to assess a need for therapy at 3 months when participants had moderate to severe pain and at 6 and 12 months when participants had low work self-efficacy, pain, impaired knee flexion ROM, and balance limitations.']

['Psm2, one of the pyrrolidinoindoline alkaloids isolated from whole Selaginella moellendorffii plants, has shown a potent antiplatelet activity. In this study, we further evaluated the antiplatelet effects of Psm2, and elucidated the underlying mechanisms.', 'Human platelet aggregation in vitro and rat platelet aggregation ex vivo were investigated. Agonist-induced platelet aggregation was measured using a light transmission aggregometer. The antithrombotic effects of Psm2 were evaluated in arteriovenous shunt thrombosis model in rats. To elucidate the mechanisms underlying the antiplatelet activity of Psm2, ELISAs, Western blotting and molecular docking were performed. The bleeding risk of Psm2 administration was assessed in a mouse tail cutting model, and the cytotoxicity of Psm2 was measured with MTT assay in EA.hy926 cells.', 'Psm2 dose-dependently inhibited human platelet aggregation induced by ADP, U4619, thrombin and collagen with IC50 values of 0.64, 0.37, 0.35 and 0.87 mg/mL, respectively. Psm2 (1, 3, 10 mg/kg) administered to rats significantly inhibited platelet aggregation ex vivo induced by ADP. Psm2 (1, 3, 10 mg/mL, iv) administered to rats with the A-V shunt dose-dependently decreased the thrombus formation. Psm2 inhibited platelet adhesion to fibrinogen and collagen with IC50 values of 84.5 and 96.5 mg/mL, respectively, but did not affect the binding of fibrinogen to GPIIb/IIIa. Furthermore, Psm2 inhibited AktSer473 phosphorylation, but did not affect MAPK signaling and Src kinase activation. Molecular docking showed that Psm2 bound to phosphatidylinositol 3-kinase β (PI3Kβ) with a binding free energy of -13.265 kcal/mol. In addition, Psm2 did not cause toxicity in EA.hy926 cells and produced only slight bleeding in a mouse tail cutting model.']

['The release and vasoconstrictor effect of endothelin-1 (ET-1) are increased after myocardial ischemia, suggesting a role for ET-1 in ischemia/reperfusion injury. However, the mechanisms of the increased vasoconstriction by ET-1 are unknown. The aim of this study was to test whether ET-1-induced release of thromboxane A2 (TXA2) contributes to the vasoconstrictor effect of ET-1 in nonischemic hearts and whether such release can increase the vasoconstrictor effect of ET-1 in postischemic reperfused hearts.', 'ET-1-induced release of TXA2 was assessed by measurement of the concentrations of its stable metabolite thromboxane B2 (TXB2) in the coronary effluent of nonischemic and reperfused isolated rat hearts before and after administration of 0.01 nmol ET-1 using an enzyme immunoassay. The contribution of ET-1-induced release of TXA2 to the vasoconstrictor effect of ET-1 was assessed by measurement of the effects of ET-1 with and without the cyclooxygenase inhibitor indomethacin or the TXA2/endoperoxide receptor antagonist SQ 30,741 using 31P magnetic resonance spectroscopy. In nonischemic hearts, ET-1 led to a small increase in TXB2 in the coronary effluent (3.9 +/- 1.5 pg/mL; n = 3), but neither indomethacin nor SQ 30,741 significantly diminished the vasoconstrictor effects of ET-1 (reduction of coronary flow, 4.0 +/- 0.4 and 4.5 +/- 0.3 mL/min, respectively, versus 4.9 +/- 0.5 mL/min for ET-1 alone; n = 8, 6, and 9, respectively). In postischemic reperfused hearts, however, ET-1 led to a greater increase in TXB2 (13.7 +/- 1.5 pg/mL; P < .05 versus nonischemic hearts; n = 3), and both indomethacin and SQ 30,741 diminished the vasoconstrictor effects of ET-1 (reduction of coronary flow, 2.6 +/- 0.3 and 2.2 +/- 0.3 mL/min, respectively, versus 4.0 +/- 0.1 mL/min for ET-1 alone; n = 8, 8, and 6, respectively; P < .05). Furthermore, indomethacin and SQ 30,741 prevented the detrimental effects of ET-1 on left ventricular developed pressure, intracellular pH, and phosphocreatine during reperfusion.']

['Enterovirus infections are major etiological factors in myocarditis and dilated cardiomyopathy. Using an experimental murine model of this disease, previous studies have shown that myocarditis susceptibility depends upon activation of T lymphocytes expressing the gamma delta T cell receptor (TcR), and that only mouse strains which accumulate gamma delta T cells in the myocardium show apoptosis of myocytes or evidence of dilated cardiomyopathy-like disease. The objective of the present studies is to demonstrate that gamma delta T cells directly induce greater Fas-dependent apoptosis of cultured myocytes than T cells expressing the alpha beta TcR.', 'Bl.Tg.E alpha mice were infected for 7 days with coxsackievirus B3 (CVB3). Hearts were removed and were either formalin-fixed, sectioned and stained with hematoxylin and eosin for inflammation, and using TdT-TUNEL for apoptosis, or were minced and collagenase digested for isolation of gamma delta+ and alpha beta+ T cells using immunomagnetic bead separation. Neonatal cultures of cardiac myocytes were isolated from mice less than 2 days old by collagenase and pancreatin digestion, and were either untreated or infected with virus. Levels of Fas (CD95) were measured using FITC-conjugated hamster anti-mouse Fas monoclonal antibody and flow cytometry. Susceptibility of myocytes to Fas-dependent killing was measured by 51Cr-release by labeled myocytes incubated for 4 h on either 3T3-mock or 3T3-FasL transfected cell monolayers. Killing by T cells was also measured in a 4 h 51Cr-release assay. Fas-dependent and perforin-dependent cytotoxicity was determined by specific blocking using either Fas-Fc or concanamycin A.', 'Virally infected myocyte cultures showed significantly enhanced Fas expression compared to uninfected cells, with maximal upregulation of Fas occurring 18-24 h after virus infection. Both infected and uninfected myocytes were selectively killed by FasL-transfected 3T3 cells but not by mock control cells. Approximately 38% of CD3+ lymphocytes isolated from the heart express the gamma delta TcR with the remainder expressing the alpha beta TcR. Both gamma delta+ and alpha beta+ T cells lysed myocyte targets. Blocking studies indicate that gamma delta+ T cells induced predominantly Fas-mediated killing, while alpha beta+ cell produced more perforin-mediated death, although these effectors were capable of Fas-dependent killing as well.']

['Airway smooth muscle (ASM) hyperplasia is a feature of asthma, and increases with disease severity. We hypothesized that this results from migration of ASM or progenitors in response to chemokines derived from ASM or mast cells within the ASM bundle.', "To examine expression of the chemokine receptor, CC chemokine receptor (CCR) 7, in vivo by ASM in patients with asthma and healthy control subjects, and by primary cultures of ASM and fibroblasts; to define expression of its ligands, CC chemokine ligand (CCL) 19 and CCL21, in bronchial biopsies, and primary cultures of ASM and mast cells; and to investigate CCR7's role in ASM migration and repair.", 'ASM was isolated from bronchoscopy and resection tissue. Receptor and chemokine expression was examined by immunohistochemistry, immunofluorescence, flow cytometry, ELISA, and reverse transcriptase-polymerase chain reaction. CCR7 function was examined by intracellular calcium measurements, chemotaxis, wound healing assays, and measurement of cell proliferation.', 'ASM, myofibroblasts, and fibroblasts expressed CCR7. CCL19, but not CCL21, was highly expressed in bronchial biopsies by mast cells and vessels in asthma of all severities, ASM in severe disease, and ex vivo ASM and mast cells. ASM CCR7 activation by CCL19-mediated intracellular calcium elevation and concentration-dependent migration, but not proliferation. Importantly, mast cell and ASM-derived CCL19 mediated ASM migration and repair.']

['Monotherapy with clopidogrel reduced the formation of transplant arteriosclerosis in a murine aortic allograft model. However, the underlying immunologic mechanisms are still unknown.', 'Fully major histocompatibility complex-mismatched C57BL/6 (H2b) donor aortas were transplanted into CBA.J (H2k) recipients and mice received different doses (1, 10, and 20 mg/kg) of clopidogrel, an antagonist of the P2Y12 ADP receptor on platelets, or control saline for 30 days. Blood was analyzed for changes in adhesion molecule and sCD40L concentrations by ELISA. Grafts were analyzed by histology, morphometry, and immunofluorescence on day 30 after transplantation. Intragraft cytokine mRNA production was analyzed by reverse-transcriptase polymerase chain reaction on day 14 after transplantation.', 'Treatment with clopidogrel resulted in significantly decreased blood concentrations of sCD40L and P-selectin after transplantation. Cellular analysis of the aortic transplant revealed fewer numbers of infiltrating dendritic cells (CD205+) and macrophages (F4/80+) after application of clopidogrel, whereas T-cells within the graft were unaltered. In addition cellular P-/E-selectin, ICAM-1, and platelet-derived-growth-factor (PDGF)-beta surface expression were significantly reduced as compared with untreated controls. Intragraft mRNA expression confirmed these results and showed significant lower production of P-/E-selectin, ICAM-1, and PDGF-beta after treatment with clopidogrel. Antiglycoprotein-Ib and antiglycoprotein VI had no beneficial effect on the development of transplant arteriosclerosis.']

['Advanced pancreatic cancer (PC) has very poor prognosis with present treatments, thus necessitating continued efforts to find improved therapeutic approaches. Both preclinical and preliminary clinical data indicate that cytokine-induced killer (CIK) cells are an effective tool against various types of solid tumors. Here, we conducted a study to determine whether CIK cell-based therapy (CBT) can improve the outcomes of advanced PC.', 'Eighty-two patients with advanced PC, whose predicted survival time was longer than 3 months, were analyzed retrospectively. Of all the patients, 57 individuals were receiving chemotherapy, while the remaining 25 individuals were treated with CBT.', 'The overall survival analysis was based on 48 deaths in the 57 patients in the chemotherapy group (84.2%) and 18 deaths in the 25 patients in the CBT group (72.0%). In the CBT group, the median overall survival time was 13.5 months, as compared to 6.6 months in the chemotherapy group (hazard ratio for death, 0.39; 95% confidence interval, 0.23 to 0.65; p\u2009<\u20090.001). The survival rate was 88.9% in the CBT group versus 54.2% in the chemotherapy group at 6 months, 61.1% versus 12.5% at 12 months, and 38.9% versus 4.2% at 18 months. The disease control rate was 68.0% in the CBT group and 29.8% in the chemotherapy group (p\u2009<\u20090.001).']

['Microvascular disease is a leading cause of cognitive impairment. Approximately 50% of people with a hip fracture have cognitive impairment.', 'We tested the hypothesis that microvascular diseases of the brain (lacunar infarcts and white matter disease [WMD]), kidney (albuminuria [≥ 30 mg/g creatinine] and albumin creatinine ratio [ACR]), and eye (retinal vascular disorders) attenuate the association of cognitive impairment with hip fracture risk.', 'The Cardiovascular Health Cognition Study.', 'Three thousand, one-hundred six participants (mean age, ∼ 79 y; 8.84 y median follow-up) with cognitive testing. Subsets received ACR testing (n=2389), brain magnetic resonance imaging scans (n = 2094), and retinal photography (n = 1098).', 'Incident hip fracture.', 'There were 488 participants (16%) with mild cognitive impairment (MCI) and 564 (18%) with dementia. There were 337 incident hip fractures, of which 19% occurred in participants with MCI and 26% in participants with dementia. Adjusted hazard ratios (HR) and 95% confidence interval for hip fracture in participants with MCI were 2.45 (1.67-3.61) and for dementia 2.35 (1.57-3.52). With doubling of ACR, the HR for fracture was attenuated in participants with dementia compared with participants with normal cognition [interaction HR 0.70 (0.55-0.91)]. No such effect was found in participants with MCI. Albuminuria, lacunar infarcts, WMD, and retinal vascular disease (RVD) did not modify the association of dementia or MCI with hip fracture risk.']

['Bronchopulmonary dysplasia (BPD) and emphysema are characterized by arrested alveolar development or loss of alveoli; both are significant global health problems and currently lack effective therapy. Bone marrow-derived mesenchymal stem cells (BMSCs) prevent adult lung injury, but their therapeutic potential in neonatal lung disease is unknown.', 'We hypothesized that intratracheal delivery of BMSCs would prevent alveolar destruction in experimental BPD.', 'In vitro, BMSC differentiation and migration were assessed using co-culture assays and a modified Boyden chamber. In vivo, the therapeutic potential of BMSCs was assessed in a chronic hyperoxia-induced model of BPD in newborn rats.', 'In vitro, BMSCs developed immunophenotypic and ultrastructural characteristics of type II alveolar epithelial cells (AEC2) (surfactant protein C expression and lamellar bodies) when co-cultured with lung tissue, but not with culture medium alone or liver. Migration assays revealed preferential attraction of BMSCs toward oxygen-damaged lung versus normal lung. In vivo, chronic hyperoxia in newborn rats led to air space enlargement and loss of lung capillaries, and this was associated with a decrease in circulating and resident lung BMSCs. Intratracheal delivery of BMSCs on Postnatal Day 4 improved survival and exercise tolerance while attenuating alveolar and lung vascular injury and pulmonary hypertension. Engrafted BMSCs coexpressed the AEC2-specific marker surfactant protein C. However, engraftment was disproportionately low for cell replacement to account for the therapeutic benefit, suggesting a paracrine-mediated mechanism. In vitro, BMSC-derived conditioned medium prevented O(2)-induced AEC2 apoptosis, accelerated AEC2 wound healing, and enhanced endothelial cord formation.']

["Medtronic's Lead Integrity Alert (LIA) software algorithm is useful for detecting abnormal parameters across various ICD-lead families. However, its utility in the assessment of the Biotronik Linox™ family of high-voltage (HV) leads is unknown.", 'We conducted a retrospective cohort study to assess the performance of the LIA algorithm to detect abnormalities and lead failure in Linox ICD-leads. All LIA-enabled Medtronic devices connected to an active Linox lead were included. The alerts were adjudicated by 2 blinded electrophysiologists and correlated with clinical data.', 'Between 2008 and 2012, data from 208 patients with 564 patient-years of follow-up were available for analysis. The median follow-up duration was 32 (IQR 21-41 months). Twenty-one LIA triggers were noted in 20 different patients. The median delay until a positive LIA was 32 months (IQR 21-41 months) postimplant with a 5-year lead survival free from LIA of 76%. Ninety-five percent (19/20) LIA alerts were true lead failures. The most common LIA triggers were short V-V intervals (85%) and nonsustained ventricular tachycardia (85%). Abrupt changes of the ICD-lead impedance occurred in 5/20 triggers. Inappropriate ICD-shocks were strongly associated with a positive LIA (30% vs. 7.4%; P = 0.006). Of the explanted Linox leads 53% had visible abnormalities. The sensitivity, specificity, and positive predictive value for lead failure in the presence of a LIA trigger were 87%, 99.5%, and 95.2%, respectively.']

['The goals of this study were to determine whether improvements in metabolic control can ameliorate the cognitive dysfunction associated with type 2 diabetes and evaluate the possibility that such improvements are mediated by changes in circulating insulin or insulin resistance.', 'This randomized double-blind trial enrolled 145 subjects at 18 centers in the U.S. Older adults with type 2 diabetes receiving metformin monotherapy received add-on therapy with either rosiglitazone, a thiazolidinedione insulin sensitizer, or glyburide. Cognitive function was assessed at baseline and week 24 using the Digit Symbol Substitution Test, the Rey Auditory Verbal Learning Test, and the Cambridge Neuropsychological Test Automated Battery.', 'Pretreatment fasting plasma glucose (FPG) in both groups was similar, and after 24 weeks both treatment groups showed similar significant reductions in FPG (2.1-2.3 mmol/l). Working memory improved with both rosiglitazone (P < 0.001) and glyburide (P = 0.017). Improvement (25-31% reduction in errors) was most evident on the Paired Associates Learning Test and was significantly correlated (r = 0.30) with improved glycemic control as measured by FPG.']

['Considering the referred beneficial effects of protein restriction on diabetic nephropathy (DN) and the role of renal endothelium in its pathogenesis, we evaluated the effect of general control nonderepressible 2 (GCN2) kinase activation, a sensor of amino acid deprivation, on known detrimental molecular pathways in primary human glomerular endothelial cells (GEnC).', 'GEnC were cultured under normal or high-glucose conditions in the presence or not of the GCN2 kinase activator, tryptophanol. Glucose transporter 1 (GLUT1) expression was assessed by western blotting and reactive oxygen species (ROS) using a fluorogenic probe. Activities of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and protein kinase C (PKC) were assessed by commercial activity assays, sorbitol colorimetrically, methylglyoxal by ELISA and O-linked β-N-acetyl glucosamine (O-GlcNAc)-modified proteins by western blotting.', "High glucose induced GLUT1 expression, increased ROS and inhibited GAPDH. Also it increased the polyol pathway product sorbitol, PKC activity, the level of the O-GlcNAc-modified proteins that produced by the hexosamine pathway and the advanced glycation endproducts' precursor methylglyoxal. Co-treatment of GEnC with tryptophanol restored the above high-glucose-induced alterations."]

['The mechanisms of osteoclast maturation and the role of rheumatoid arthritis (RA) synovial fibroblasts in the control of osteoclastogenesis remain unclear. The purpose of this study was to determine the humoral factors that influence osteoclast differentiation resulting from mutual interactions between osteoclast progenitor cells and synovial fibroblasts.', 'The cloned mouse macrophage cell line RAW 264.7 or isolated human CD14+ monocytes were cocultured with RA or osteoarthritis (OA) synovial fibroblasts in the presence of RANKL. Osteoclasts were visualized by staining for tartrate-resistant acid phosphatase (TRAP), and their functions were evaluated by bone resorption assay. Transforming growth factor beta (TGFbeta) and osteoprotegerin (OPG) levels were measured by enzyme-linked immunosorbent assay. Expression of pSmad2 and Smad7 was analyzed by Western blotting.', 'RANKL-mediated osteoclast formation was observed in cocultures of RAW cells with RA synovial cells, but not with OA synovial cells. This formation was inhibited by TGFbeta receptor kinase inhibitor or neutralizing TGFbeta antibody. Human CD14+ monocytes showed the same results with RAW 264.7, and bone resorption activity was consistent with osteoclast formation. RA synovial fibroblasts produced TGFbeta in response to cell-cell contact with RAW cells in a RANKL-dependent manner. TGFbeta reduced OPG production by RA synovial fibroblasts, but dose-dependently increased OPG secretion in OA synovial fibroblasts. TGFbeta decreased the expression of pSmad2 and increased the expression of Smad7 in RA synovial fibroblasts, but not OA synovial fibroblasts.']

['It is not clear whether risk for hepatocellular carcinoma can be accurately determined from long-term changes in serum levels of hepatitis B virus (HBV) DNA or alanine aminotransferase (ALT).', 'We measured serum levels of HBV DNA and ALT at enrollment and during follow-up analysis of 3160 participants in the REVEAL-HBV study. Development of hepatocellular carcinoma was determined from follow-up examinations and computerized linkage with National Cancer Registry and National Death Certification profiles. Multivariate-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox regression models.', 'During 38,330 person-years of follow-up, 81 participants developed hepatocellular carcinoma (incidence rate, 211.3/100,000 person-years). The risk for hepatocellular carcinoma was only slightly higher for participants whose follow-up levels of HBV DNA spontaneously decreased to <10,000 copies/mL compared with those with baseline levels of HBV DNA<10,000 copies/mL (control group; HR, 2.25; 95% CI, 0.68-7.37). Compared with the control group, the HRs (95% CI) for long-term levels of HBV DNA that persisted at 10,000 to 100,000 copies/mL, decreased to/persisted at 100,000 to 1,000,000 copies/mL, or decreased to/persisted at 1,000,000 to 10,000,000 copies/mL were 3.12 (1.09-8.89), 8.85 (3.85-20.35), and 16.78 (7.33-38.39), respectively. A gradient in ALT level was significantly associated with hepatocellular carcinoma risk: from all low-normal, to ever high-normal, to transient abnormal, to persistent abnormal (Ptrend<.001).']

["To evaluate patients' self-assessment of their symptoms and cosmetic appearance after fluorescein-potentiated argon laser treatment (FPAL) for corneal inflammation associated with neovascularization. To describe the objective effects of FPAL therapy on established corneal neovascularization with secondary corneal edema and lipid keratopathy.", 'Fifteen patients with corneal neovascularization resulting from various infectious and traumatic etiologies were enrolled in an open, nonrandomized pilot study. Treatment consisted of repeated sessions of intravenous fluorescein, a photosensitizer, combined with blue-green argon laser applications to abnormal corneal vessels. Patients completed a written survey to grade their symptoms and cosmetic appearance prior to treatment and at the end of the follow-up period. Objective changes in signs after FPAL treatment were described by two nonmasked ophthalmologists after slit-lamp examinations and review of serial corneal photographs.', "Clinical symptoms of blurred vision (p <or= 0.003), photophobia (p <or= 0.03), and cosmetic appearance ( p <or= 0.02) were found to be significantly improved by the patient's subjective assessment survey. There was a trend toward pain reduction (p <or= 0.06) but no apparent reduction in tearing or foreign body sensation (p <or= ns). Objective signs of corneal edema, neovascularization, and lipid keratopathy appeared to be reduced after FPAL therapy."]

['Epithelial-mesenchymal transition (EMT) increases cell migration and is implicated in cancer cell invasion and metastasis. We have previously described the involvement of the transcription factors, nuclear factor I-C2 (NFI-C2) and Forkhead box F1 (FoxF1), in the regulation of EMT and invasion during breast tumor progression. NFI-C2 counteracts these processes and FoxF1 is a directly repressed target of NFI-C2. FoxF1 induces EMT and invasiveness and enhances xenograft tumorigenicity in nude mice. Here we identify oppositely regulated targets of NFI-C2 and FoxF1 involved in these processes and further study a possible role for FoxF1 in tumorigenesis.', 'We used Affymetrix microarray to detect changes in the transcriptome of a mouse mammary epithelial cell line upon overexpression of NFI-C2 or FoxF1. To elucidate the effects and signaling events following FoxF1 overexpression we investigated in vitro invasion capacity and changes in transcription and protein expression resulting from RNAi and inhibitor treatment.', 'The extracellular matrix enzyme lysyl oxidase (LOX) was negatively regulated by NFI-C2 and positively regulated by FoxF1, and upregulation of LOX following FoxF1 overexpression in mouse mammary epithelial cells increased in vitro cell invasion. In the nuclei of FoxF1-overexpressing cells, the phosphorylation of Smad2 decreased, while that of p38 increased. Depletion of LOX by RNAi enhanced phosphorylation of Smad2 by a focal adhesion kinase (FAK)-dependent mechanism. In addition, induced expression of FoxF1 in a non-malignant human mammary epithelial cell line showed that the increase in LOX transcription and the suppression of Smad2 activity are early effects of FoxF1.']

['The V600E BRAF mutant plays an important role in the pathogenesis of papillary thyroid cancer (PTC) and is associated with loss of expression of thyroid iodide-metabolizing genes. This study was done to investigate the restorability of expression of these genes by suppressing the BRAF/extracellular signal-regulated kinase kinase (MEK)/mitogen-activated protein (MAP) kinase pathway in V600E BRAF-harboring thyroid cells and to explore the mechanisms involved.', 'We used inducible expression of V600E BRAF, small interfering RNA transfection, and MEK-specific inhibitor to alter the MAP kinase pathway activities and subsequently examined the changes in expression, promoter activities, and methylation status of thyroid genes.', 'MEK inhibitor U0126 or cessation of V600E BRAF expression in PCCL3 cells restored expression of thyroid genes silenced by induced expression of V600E BRAF. U0126 also restored the expression of these genes in V600E BRAF-harboring PTC-derived NPA cells. Knockdown of BRAF by specific small interfering RNA restored expression of some of these genes in NPA cells. Luciferase reporter assay using thyroid-stimulating hormone receptor gene as a model showed that the promoter activity was modulated by the MAP kinase pathway. Promoter methylation in association with DNA methyltransferase expression played a role in gene silencing by MAP kinase pathway in NPA cells.']

['To investigate the placental expression of angiopoietin (Ang)-1, Ang-2 and their receptor, Tie-2, in preeclampsia (PE) with or without intrauterine growth restriction (IUGR).', 'Case-control study including placentas from 28\xa0PE pregnancies, 30\xa0PE-IUGR pregnancies and 40 controls. The expression status of the genes was evaluated by quantitative real-time PCR.', 'In both PE and PE-IUGR groups, compared to the control group, there was significantly higher expression of Ang-2 (p\xa0<\xa00.001) and Tie-2 (p\xa0=\xa00.008) and lower expression of Ang-1 (p\xa0=\xa00.001). The magnitude of the difference was similar for Ang-1 for both groups, whereas the magnitude of the differences was higher for Ang-2 and Tie-2 in PE-IUGR group compared to controls. Ang-2 and Tie-2 were correlated in both PE (r\xa0=\xa00.8602, p\xa0<\xa00.001) and PE-IUGR (r\xa0=\xa00.6342, p\xa0<\xa00.001) groups. In PE-IUGR group, Ang-1 was associated to Ang-2 (r\xa0=\xa00.3458, p\xa0=\xa00.0452) and Tie-2 (r\xa0=\xa00.4448, p\xa0=\xa00.0084). Log10Ang-1 but not Ang-2 was gestational age dependent (R2\xa0=\xa00.40, p\xa0<\xa00.001). After conversion in Multiples of the Median (MoM) log10 MoM Ang-1 was reduced in the PE group (mean\xa0=\xa0-0.8181, p\xa0<\xa00.001) and the PE-IUGR group (mean\xa0=\xa0-1.2583, p\xa0<\xa00.001) compared to control group (mean\xa0=\xa0-0.0924).']

['Thyroid hormone (TH) is essential for the developing brain, and because the fetal thyroid develops relatively late in gestation, the maternal TH supply is critical for fetal brain development. However, if the mother has hypothyroidism during pregnancy, fetal brain and neuropsychological development may be compromised. Rodents experiencing maternal TH insufficiency show abnormal corpus callosum (CC) morphology, but it is not known if children born to women treated for hypothyroidism (HYPO) show similar effects. The purpose of the current study was to investigate HYPO for CC morphology and morphometry and to determine whether any specific CC abnormalities were associated aspects of maternal hypothyroidism and were correlated with reduced neuropsychological functioning in the children.', "ANALYZE software was used to trace CCs in archived magnetic resonance imaging scans from 22 HYPO and 22 matched controls. Areas of two sub-regions and six segments and different shape metrics (angles, lengths, ratios) were determined. CC parameters were correlated with maternal thyrotropin (TSH) values and number of hypothyroid trimesters as well as the child's neuropsychological test performance.", 'HYPO showed a smaller anterior CC and genu and larger posterior CC and splenium areas than controls as well as shape abnormalities in genu and splenium. Results were correlated with the duration of maternal hypothyroidism. Executive function skills were positively associated with genu size in HYPO, while verbal comprehension skills were negatively associated with splenium and overall posterior CC sizes.']

['Peripheral clock genes show a circadian rhythm is correlated with the timing of feeding in peripheral tissues. It was reported that these clock genes are strongly regulated by insulin action and that a high-fat diet (HFD) intake in C57BL/6J mice for 21days induced insulin secretion during the dark phase and reduced the circadian rhythm of clock genes. In this study, we examined the circadian expression patterns of these clock genes in insulin-resistant animal models with excess secretion of insulin during the day.', 'We examined whether insulin resistance induced by a HFD intake for 80days altered blood parameters (glucose and insulin concentrations) and expression of mRNA and proteins encoded by clock and functional genes in the liver using male ICR mice.', 'Serum insulin concentrations were continuously higher during the day in mice fed a HFD than control mice. Expression of lipogenesis-related genes (Fas and Accβ) and the transcription factor Chrebp peaked at zeitgeber time (ZT)24 in the liver of control mice. A HFD intake reduced the expression of these genes at ZT24 and disrupted the circadian rhythm. Expression of Bmal1 and Clock, transcription factors that compose the core feedback loop, showed circadian variation and were synchronously associated with Fas gene expression in control mice, but not in those fed a HFD.']

['Accumulating evidence supports a role of 4-hydroxynonenal (4HNE) in oxidative-stress related diseases, but its specific contribution to disease development remains to be clarified. Further to our finding of high circulating 4HNE-protein thioether adducts (4HNE-P) in spontaneously hypertensive rats (SHRs), we aimed at correlating 4HNE-P with cardiac function and testing the impact of antioxidant therapy.', 'The lipoperoxidation inhibitor probucol (10 mg/kg/day) or vehicle (corn oil) were administered daily (i.p.) for 4 weeks in 18-week-old SHRs (9 rats/group). Cardiac functions were assessed by echocardiography and 4HNE-P by gas chromatography/mass spectrometry.', 'Diastolic dysfunction worsened in SHRs receiving vehicle as reflected by changes (P < 0.05) in indexes of left ventricular relaxation (increased isovolumic relaxation time) and compliance (increased E-wave deceleration rate; EDR). Higher circulating 4HNE-P correlated with diastolic dysfunction (EDR: R(2) = 0.518; P < 0.001) and heart rate (R(2) = 0.225; P < 0.05). Probucol prevented the deterioration of diastolic function, while lowering the mean and median of circulating 4HNE-P by 21% and 35%, respectively.']

['We have previously demonstrated that human serum can suppress the proliferative response in autologous mixed lymphocyte reaction (AMLR) in which phytohemagglutinin (PHA)-activated T lymphoblasts act as stimulators (T-TPHA AMLR). The aim of the present work was to determine whether pregnancy serum (PS) possesses an inhibitory capacity similar or different in magnitude.', 'Sixteen PS were added to T-TPHA AMLR cultures and the proliferative response was compared with that in the presence of human serum. The effect of PS on the IL-2 dependent proliferation of PHA-activated T Lymphoblasts was examined as well.', 'PS induced a significantly more pronounced suppression of T-TPHA AMLR than human serum (P < 0.05). One PS tested was not inhibitory but rather stimulatory. This PS was obtained from a woman who subsequently had IUGR. The inhibition is related to the existence of a serum inhibitory factor and not to the lack of a serum supporting factor. PS inhibited not only T-TPHA AMLR of the same woman but also T-TPHA AMLR of other individuals as well, implying that the inhibitor is a non-MHC restricted factor. IL-2 dependent cell proliferation was not inhibited by PS, implying that the inhibitor detected in T-TPHA AMLR is not a general cell proliferation inhibitor.']

['Endometriosis is a gynecological condition that is characterized by extreme abdominal pain and also decreased fertility. Regulatory T cells (Tregs) have immunosuppressive activity critical for embryonic implantation and likewise the acceptance of tissue engraftment. Utilizing the induced non-human primate (Papio anubis) model of endometriosis, we hypothesize that endometriosis decreases the peripheral and endomet rial Treg profile, whereas ectopic lesions have increased Treg localization.', 'Peripheral blood and endometrium were obtained throughout the menstrual cycle prior to and after induction of disease. Animals were randomly assigned to control (n = 7) or diseased (n = 16) treatment groups. Endometriosis was induced by i.p. injection of autologous menstrual tissue for 2 consecutive months during menses. Peripheral blood and endometrial tissue were collected at d9-11PO at 1, 3, 6, 9, 12 and 15 months post-induction of disease for fluorescence-activated cell sorting, quantitative RT-PCR and immunohistochemistry. Ectopic lesions were excised at 1 and 6 months post-inoculation and also harvested at necropsy (15 months) and processed for RNA of IHC. Identification of Tregs through analysis of FOXP3 expression was conducted utlilizing several methodologies. Differences were determined by non-parametric statistical analysis between all treatment groups and time points.', 'In control animals, the proportion of peripheral natural Tregs (nTregs) was reduced (P < 0.05) during the mid- and late secretory stages of the menstrual cycle compared with menses. The induction of disease decreased peripheral Treg expression at early time points (P < 0.05) and this remained low throughout the time course, compared with the pre-inoculatory level of an individual. FOXP3 gene expression and Treg populations were also decreased in the eutopic endometrium (P < 0.05) compared with control animals, whereas these parameters were increased in ectopic lesions (P < 0.05), compared with the eutopic endometrium.']

['To examine the association of blood antioxidants with cataract.', 'Cross-sectional study of people aged >or=50 years identified from a household enumeration of 11 randomly sampled villages in North India. Participants were interviewed for putative risk factors (tobacco, alcohol, biomass fuel use, sunlight exposure, and socioeconomic status) and underwent lens photography and blood sampling. Lens photographs (nuclear, cortical, and posterior subcapsular) were graded according to the Lens Opacities Classification System (LOCS II). Cataract was defined as LOCS II grade >or=2 for any opacity or ungradable, because of dense opacification or history of cataract surgery. People without cataract were defined as LOCS II <2 on all three types of opacity, with absence of previous surgery.', 'Of 1443 people aged >or=50 years, 94% were interviewed, 87% attended an eye examination, and 78% gave a blood sample; 1112 (77%) were included in the analyses. Compared with levels in Western populations, antioxidants were low, especially vitamin C. Vitamin C was inversely associated with cataract. Odds ratios (OR) for the highest (>or=15 micromol/L) compared with the lowest (<or=6.3 micromol/L) tertile were 0.64, (95% confidence interval [CI] 0.48-0.85; P < 0.01). Tertiles of zeaxanthin (P < 0.03), alpha-carotene (P < 0.05), and retinol (P < 0.02) were associated with decreased odds of cataract. In analysis of continuous data, significant inverse associations were found for vitamin C, zeaxanthin, lutein, lycopene, alpha- and beta-carotene, and beta-cryptoxanthin, but not for alpha- or gamma-tocopherol.']

['The purpose of the study was to assess ongoing pregnancy rates across groups of patients treated by IVF, which were defined according to criteria aimed at the prevention of premature LH surge and used for initiating GnRH antagonist.', 'This is a prospective observational cohort study. During the last 3 years, in IVF-ICSI patients undergoing controlled ovarian stimulation (COS) with the antagonist protocol, the antagonist administration was initiated according to at least one of the following patient-specific criteria: (i) at least one follicle measuring >14 mm; (ii) estradiol levels >600 pg/ml; and (iii) LH levels >10 IU/l. Based upon these criteria, 208 cases of normal responders were analysed and categorized into three groups according to the starting day of the regimen: group D4 (n = 40) for day 4, group D5 (n = 98) for day 5 and group D6 (n = 70) for day 6. The main outcome measure was the ongoing pregnancy rate per started cycle.', 'The total number of patients in the D4 and D5 groups (138 out of 208), who received the antagonist earlier, was considerably larger compared with that of D6 (70 out of 208). Ongoing pregnancy rates were 37.5, 34.7 and 18.6% for groups D4, D5 and D6, respectively. Patients who initiated the GnRH antagonist on days 4 and 5 had statistically significant higher pregnancy rates compared with day 6. Rapid response, causing earlier antagonist administration initiation, according to the proposed criteria for the prevention of premature LH surges, and the absence of premature luteinization, as evidenced by normal progesterone levels on HCG day, were found to be independent positive predictive factors for favourable IVF outcome.']

['Mean platelet volume (MPV), an indicator of platelet activation, has been shown to be elevated in patients with coronary artery disease (CAD) in some studies. Insulin resistance contributes to increased platelet activation and it is one of the risk factors for CAD. The aim of this study was to assess the relationship between insulin resistance and MPV in non-obese, non-diabetic patients with CAD.', 'Seventy-seven non-obese, non-diabetic CAD patients were divided into two groups, insulin resistant and insulin sensitive according to the homeostasis model assessment insulin resistance index (HOMA-IR). The insulin-resistant group was composed of 45 patients (30 males/15 females; mean age 59.8±11.1 years). The insulin-sensitive group was composed of 32 patients (17 males/15 females; mean age 58.9±12.2 years).', 'Insulin and HOMA-IR values were significantly higher in insulin-resistant CAD patients than in insulin-sensitive CAD patients. The MPV values were significantly higher in insulin-resistant CAD patients than in insulin-sensitive CAD patients (8.6±1.0 fl vs. 8.0±0.7 fl; respectively, p=0.01). The MPV was poorly correlated with HOMA-IR (r=0.30, p=0.054) and insulin (r=0.22, p=0.053).']

['The objective of this work was to determine the effect of an androgen agonist, R1881, on intracellular cholesterol synthesis and esterification in androgen-sensitive (AS) prostate cancer (LNCaP) cells.', 'We investigated the activity and expression of cholesterol metabolism enzymes, HMG-CoA-reductase and ACAT in the LNCaP and PC-3 (androgen-independent control) models.', 'Microsomal PC-3 HMG-CoA-reductase activity was increased with R1881 despite having similar cholesterol levels while increased cholesterol levels in microsomes from LNCaPs treated with R1881 (L+) were associated with increased HMG-CoA reductase activity. Increased intracellular cholesteryl esters (CE) found in (L+) were not associated with an increased ACAT1 activity. There was no effect from androgen treatment on ACAT1 protein expression in theses cells; however, ACAT2 expression was induced upon R1881 treatment. In contrast, we found an increase in the in vitro ACAT1 activity in PC-3 cells treated with androgen (P+). Only ACAT1 expression was induced in P+. We further assessed the expression of STAT1 alpha, a transcriptional activator that modulates ACAT1 expression. STAT1 alpha expression and phosphorylation were induced in P+. To determine the role of the AR on ACAT1 expression and esterification, we treated PC-3 cells overexpressing the androgen receptor with R1881 (PAR+). AR expression was decreased in PAR+ cells; ACAT1 protein expression and cholesterol ester levels were also decreased, however, ACAT2 remained unchanged. STAT1 alpha expression was decreased in PAR+.']

['We aimed to investigate whether high-sensitive cardiac troponin T (hs-cTnT) is associated with all-cause and cardiovascular mortality in stable type 2 diabetes (T2D) outpatients treated in primary care.', 'Cardiac troponin T was measured with a high-sensitive assay at baseline in patients with T2D participating in the observational ZODIAC study. Cox proportional hazards models were used to investigate the relationship between hs-cTnT and mortality with adjustment for selected confounders. Risk prediction capabilities of hs-cTnT were assessed with Harrell C statistics.', 'Complete baseline data were available for 1,133 patients. During median follow-up of 11 (7-14) years, 513 (45%) patients died, of which 218 (42%) died of cardiovascular causes. Of the patients with undetectable hs-cTnT levels (<3 ng/L), only 23% died, compared with 58% with low detectable levels (3-14 ng/L) and 84% with raised levels (≥14 ng/L). Natural log hs-cTnT was significantly associated with all-cause mortality (hazard ratio 1.30, 95% CI 1.19-1.42) and cardiovascular mortality (hazard ratio 1.33, 95% CI 1.15-1.53), independent of potential confounders. The Harrell C statistic for the crude model of hs-cTnT was 0.72 (95% CI 0.70-0.75) for all-cause mortality and 0.74 (95% CI 0.71-0.77) for cardiovascular mortality.']

['Using a diet-induced obesity (DIO) mouse model, we investigated the antidiabetic effect of Labrador tea [Rhododendron groenlandicum (Oeder) Kron and Judd], a beverage and medicinal tea used by the Cree Nations of northern Quebec.', "C57BL6 mice were divided into five groups and given standard chow (~4 % of lipids) or high-fat diet (~35 % of lipids) for 8 weeks until they became obese and insulin resistant. Treatment began by adding the plant extract at three doses (125, 250 and 500 mg/kg) to the high-fat diet for another 8 weeks. At the end of the study, insulin-sensitive tissues (liver, skeletal muscle, adipose tissue) were collected to investigate the plant's molecular mechanisms.", 'Labrador tea significantly reduced blood glucose (13 %), the response to an oral glucose tolerance test (18.2 %) and plasma insulin (65 %) while preventing hepatic steatosis (42 % reduction in hepatic triglyceride levels) in DIO mice. It stimulated insulin-dependent Akt pathway (55 %) and increased the expression of GLUT4 (53 %) in skeletal muscle. In the liver, Labrador tea stimulated the insulin-dependent Akt and the insulin-independent AMP-activated protein kinase pathways. The improvement in hepatic steatosis observed in DIO-treated mice was associated with a reduction in inflammation (through the IKK α/β) and a decrease in the hepatic content of SREBP-1 (39 %).']

['To determine the ability of voriconazole to inhibit the formation of biofilms.', 'A total of 38 blood isolates of Candida spp. (8 Candida albicans, 10 Candida tropicalis, 10 Candida glabrata, 7 Candida parapsilosis sensu stricto and 3 Candida orthopsilosis) and C. albicans ATCC 90028 and ATCC 64548 were assessed. Biofilm formation was quantified using XTT reduction assays. The inhibition of biofilm formation was determined (i) in the presence of 0.06 and 0.25 mg/L voriconazole, and (ii) on surfaces previously coated with 0.06, 0.25, 1, 4 and 16 mg/L voriconazole.', 'Voriconazole reduced biofilm formation under both conditions, the extent depending on the species, isolate and drug concentration. In the presence of 0.25 mg/L, the highest reduction was found for C. parapsilosis (79%\u200a±\u200a8.6%), followed by C. albicans (64.5%\u200a±\u200a6.3%), C. tropicalis (53.3%\u200a±\u200a13.1%) and C. glabrata (23.8%\u200a±\u200a11.2%). This reduction was significant (P\u200a<\u200a0.05) for all isolates tested. After coating the wells with voriconazole, biofilm formation was reduced in all Candida spp. examined, C. albicans being the species with the highest reduction (68.8% with 16 mg/L) and C. parapsilosis complex and C. glabrata the lowest.']

['Obstructive nephropathy is a primary cause of renal failure in infancy. Chronic unilateral ureteral obstruction (UUO) in the neonatal rat results in reduced renal expression of epidermal growth factor (EGF), renal tubular epithelial (RTE) cell apoptosis and interstitial fibrosis. We wished to determine whether these changes could be prevented by exogenous administration of EGF.', 'Thirty-three Sprague-Dawley rats underwent UUO within the first 48 hours of life, and received daily injections of either EGF (0.1 mg/kg/day) or saline (control) for the following seven days, after which obstructed and intact opposite kidneys were removed for study. These were compared to 11 sham-operated rats that received either no injections, EGF injections, or saline injections. Renal cell proliferation was determined by proliferating cell nuclear antigen, apoptosis was measured by the TUNEL technique, and the distribution of vimentin, clusterin, transforming growth factor-beta 1 (TGF-beta 1), and alpha-smooth muscle actin were determined by immunohistochemistry. Tubular dilation, tubular atrophy, and interstitial collagen deposition were quantitated by histomorphometry.', 'Compared to controls, EGF treatment increased RTE cell proliferation in the obstructed kidney by 76%, decreased apoptosis by 80%, and reduced vimentin, clusterin and TGF-beta 1 immunostaining (all P < 0.05). EGF treatment reduced tubular dilation by 50%, atrophic tubules by 30%, and interstitial fibrosis by 50% (all P < 0.05). There was no significant effect of EGF on renal alpha smooth muscle actin distribution. There was no effect of saline or EGF injections on kidneys from sham-operated rats for any of the parameters studied.']

['To assess drug-compliance observed among patients with suspected streptococcal pharyngitis treated with twice-daily antibiotic regimens (b.i.d.) and others with thrice-daily regimens (t.i.d.).', "A prospective study in the primary care setting was designed in which patients with pharyngitis and three or more Centor criteria, non-allergic to beta-lactam agents, treated with several b.i.d and t.i.d antibiotic regimens based on doctor's choice, were recruited. Patient compliance was assessed with electronic monitoring.", 'A total of 113 patients were enrolled (64 in the t.i.d. group and 49 in the b.i.d. group). Mean openings ranged from 70.3 to 83.3% of the total amount of pills. All the parameters analysed indicated significantly worse compliance with the t.i.d. regimens. Eleven patients allocated to the t.i.d. group took at least 80% of the pills (17.2%), this being significantly lower than those who received b.i.d. antibiotics (59.2%; p < 0.001). The percentage of patients who opened the Medication Event Monitoring System (MEMS) container the satisfactory number of times a day was systematically lower among t.i.d. regimens, this being statistically significant from day three (p < 0.05). Patients assigned to t.i.d. regimens more frequently forgot the afternoon dose.']

['Breast milk has been shown to be associated with greater success with regard to weaning children with intestinal failure off parenteral nutrition (PN). There are only a few studies investigating the role of breast milk in decreasing PN-associated liver disease (PNALD). The aim of our study was to determine whether breast milk is better than formula milk in preventing PNALD in infants receiving PN for >4 weeks.', 'We conducted a retrospective analysis of newborns requiring prolonged parenteral nutrition. We divided the sample into 3 different groups (exclusive breast-feeding, exclusive formula-feeding, and mixed feeding. We compared baseline characteristics, feeding profiles and liver function tests, and liver enzymes among the 3 groups.', 'Among infants receiving PN for >4 weeks, we found that infants who were fed only breast milk were significantly less likely to develop PNALD (34.6%) compared with those who were fed only formula milk (72.7%; P = 0.008). The mean maximum conjugated bilirubin (P = 0.03) and the mean maximum aspartate aminotransferase were significantly lower in the breast-fed group (P = 0.04) compared with the formula-fed group. Among the mixed-feeding group, infants who received a higher percentage of breast milk showed a significant negative correlation with the mean maximum conjugated bilirubin. (Pearson correlation -0.517, P = 0.027). The mean number of days receiving PN and the average daily lipid intake in the 2 groups was not significantly different.']

['Epithelial cells cultured from prostatic acini do not demonstrate significant (P > 0.05) growth response to the testosterone metabolite dihydrotestosterone (DHT) at concentrations of 0.001-10.0 nM. In addition, the nonsteroidal antiandrogen hydroxyflutamide (HO-F) does not influence primary epithelial cell proliferation in this concentration range.', 'Northern blotting carried out with an androgen reception (AR)-specific cDNA probe indicated that the extent of AR gene expression in six unpassaged primary prostatic epithelial cell cultures was insufficient to elicit a detectable signal upon autoradiography. However, RT/PCR analysis of total RNA using two sets of intron-spanning androgen receptor (AR) primers demonstrates the presence of full-length receptor transcripts in two BPH-derived epithelial cell cultures (BPH1 and BPH2) as well as a carcinoma-derived culture (CaP1).', 'AR-positive LNCaP cells transfected with the AR reporter plasmid pMMTV/SPAP exhibit significant increases (P < 0.05) in SPAP production upon treatment with DHT. pMMTV/SPAP-transfected primary epithelial cells exhibit no such response when pulsed with either androgen or anti-androgen.']

['Activity of the tumour-suppressor gene PTEN is reduced in different types of cancer and implicates non-responsiveness to targeted therapy. This study evaluates the gene and protein status of PTEN in salivary gland carcinomas.', 'A total of 287 carcinomas of the major and minor salivary glands were investigated for phosphatase and tensin homologue located on chromosome 10 (PTEN) deletion and loss of PTEN expression using fluorescence in situ hybridisation (FISH) and immunohistochemistry (IHC), respectively. Results were correlated to clinicopathological parameters, long-term survival, epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) (IHC and FISH) status of the tumours.', 'Hemizygous deletions of PTEN were found in 35 out of 232 (15.1%) carcinomas, while homozygous deletions were observed in 17 out of 232 (7.3%) tumours. Phosphatase and tensin homologue located on chromosome 10 deletion was common in certain histological subtypes and especially homozygous deletion was associated with high-grade malignancy, lymph node metastases and unfavourable long-term prognosis (P<0.001). Loss of PTEN expression was present in 59 out of 273 (21.6%) carcinomas and was significantly correlated to genomic PTEN deletion, high-grade malignancy (P<0.001), increased tumour size (P=0.036), lymph node metastases (P=0.007) and worse disease-specific survival (P=0.002). Genomic PTEN deletion, in particular homogenous deletion (P<0.001) predominantly occurred in tumours with increased gene copy number of EGFR (60.0%) and/or amplification of HER2 (63.6%). Loss of PTEN expression was frequently found in tumours overexpressing EGFR (28.6%) and/or HER2 (52.6%).']

['Long QT syndrome type 3 (LQT3) is a lethal disease caused by gain-of-function mutations in the SCN5A gene, coding for the alpha-subunit of the sodium channel NaV1.5. Mexiletine is used to block late sodium current and to shorten QT interval in LQT3 patients.', 'The aim of this study was to determine whether mexiletine prevents arrhythmic events (arrhythmic syncope, aborted cardiac arrest, or sudden cardiac death) in LQT3 patients.', 'The endpoint of this retrospective cohort study, which studied consecutive LQT3 patients who were referred to our center and treated with mexiletine, was to evaluate the antiarrhythmic efficacy of mexiletine by comparing the number of arrhythmic events per patient and the annual rate of arrhythmic events during observation periods of equal duration before and after the beginning of therapy with mexiletine.', 'The study population comprised 34 LQT3 patients, 19 (56%) of whom were male. The median age at beginning of treatment with mexiletine was 22 years, and median QTc interval before therapy 509 ms. The median duration of oral mexiletine therapy was 36 months, at an average daily dose of 8 ± 0.5 mg/kg. Mexiletine significantly shortened QTc (by 63 ± 6 ms; p < 0.0001) and reduced the percentage of patients with arrhythmic events (from 22% to 3%; p = 0.031), the mean number of arrhythmic events per patient (from 0.43 ± 0.17 to 0.03 ± 0.03; p = 0.027), and the annual rate of arrhythmic events (from 10.3% to 0.7%; p = 0.0097).']

['Intra-arterial (IA) nicardipine is often used to treat cerebral vasospasm associated with subarachnoid hemorrhage (SAH). While hypotension has been noted to be a dose-limiting side effect of intravenous infusions, this has seldom been reported for IA administration.', "We reviewed a consecutive series of patients who received IA nicardipine for SAH-associated vasospasm. Nicardipine was titrated to angiographic response, with blood pressure and intracranial pressure monitoring. We analyzed data using Wilcoxon signed rank, Student's t-test, Spearman's correlation, and χ(2) statistics as appropriate. A P value <0.05 was considered significant.", 'Thirty patients underwent 50 procedures in which nicardipine was the sole chemical vasodilator (median dose, 15\xa0mg). Median mean arterial pressures (MAP) decreased from 118 to 100\xa0mmHg (P\xa0<\xa00.001), with an intra-operative low of 80\xa0mmHg. Both intra-operative and post-operative decreases in MAP were directly related to nicardipine dose (r (s)\xa0=\xa00.352, P\xa0=\xa00.022 and r (s)\xa0=\xa00.308, P\xa0=\xa00.047, respectively). Hypotension (MAP\xa0<\xa070\xa0mmHg) occurred in 22%, and 44% required initiation of or increases in vasopressor therapy. After the first treatment, 11 of 16 patients treated with vasodilator therapy alone, and 5 of 14 patients who underwent additional balloon angioplasty (68.8 vs. 35.7%, P\xa0=\xa00.141), required further endovascular treatments due to recurrent vasospasm on subsequent days.']

['The gut microbiome, a dynamic bacterial community that interacts with the host, is integral to human health because it regulates energy metabolism and immune functions. The gut microbiome may also play a role in risks from environmental toxicants.', 'We investigated the effects of polychlorinated biphenyls (PCBs) and exercise on the composition and structure of the gut microbiome in mice.', 'After mice exercised voluntarily for 5 weeks, they were treated by oral gavage with a mixture of environmentally relevant PCB congeners (PCB153, PCB138, and PCB180; total PCB dose, 150 µmol/kg) for 2 days. We then assessed the microbiome by determination of 16S rRNA using microarray analysis.', 'Oral exposure to PCBs significantly altered the abundance of the gut microbiome in mice primarily by decreasing the levels of Proteobacteria. The activity level of the mice correlated with a substantial shift in abundance, biodiversity, and composition of the microbiome. Importantly, exercise attenuated PCB-induced changes in the gut microbiome.']

['Endothelial dysfunction is an early step in the development of atherosclerosis. Increased formation of superoxide anions by NADPH oxidase Nox1, 2, and 5 reduces nitric oxide availability and can promote endothelial dysfunction. In contrast, recent evidence supports a vasoprotective role of H2O2 produced by main endothelial isoform Nox4. Therefore, we analysed the impact of genetic deletion of Nox4 on endothelial dysfunction and atherosclerosis in the low-density lipoprotein receptor (Ldlr) knockout model.', 'Ex vivo analysis of endothelial function by Mulvany myograph showed impaired endothelial function in thoracic aorta of Nox4(-/-)/Ldlr(-/-) mice. Further progression of endothelial dysfunction due to high-fat diet increased atherosclerotic plaque burden and galectin-3 staining in Nox4(-/-)/Ldlr(-/-) mice compared with Ldlr(-/-) mice. Under physiological conditions, loss of Nox4 does not influence aortic vascular function. In this setting, loss of Nox4-derived H2O2 production could be partially compensated for by nNOS upregulation. Using an innovative optical coherence tomography approach, we were able to analyse endothelial function by flow-mediated vasodilation in the murine saphenous artery in vivo. This new approach revealed an altered flow-mediated dilation in Nox4(-/-) mice, indicating a role for Nox4 under physiological conditions in peripheral arteries in vivo.']

['Arterial stiffness may contribute to left ventricular hypertrophy (LVH). This study was conducted to evaluate the independent factor of LVH and the quantification of LVH by electrocardiogram (ECG) to predict the degree of aortic stiffness using brachial-ankle pulse wave velocity (baPWV) in subjects with hypertension.', 'A total of 984 consecutive patients who were diagnosed as having essential hypertension were entered into the study. baPWV determination, ECG and blood sampling were performed after a 12-hour overnight fast. LVH was diagnosed using electrocardiography; Romhilt-Estes point score was subsequently calculated. Participants were separated into LVH and non-LVH groups. Additional factors associated with LVH were examined using multivariate analyses.', 'The non-LVH groups were younger (P = 0.001), had less men (P = 0.001), lower systolic and diastolic blood pressure and pulse pressure (P < 0.001 for each) and lower baPWV (P < 0.001). Stepwise multiple logistic regression analysis demonstrated that sex, age, systolic blood pressure and baPWV are independent factors. Using a baPWV value of 1825 cm/sec, the area under the receiver operating characteristic curve was 0.644 and the highest discriminating sensitivity and specificity were 60% and 65%, respectively.']

['Endothelial progenitor cells (EPCs) comprise a heterogeneous population of cells, which improve therapeutic neovascularization after ischemia. The neovascularization-promoting potential of progenitor cells depends on survival and retention of the infused cells to the tissue. Caspases mediate apoptosis but are also involved in other critical biological processes. Therefore, we aimed to address the role of caspases in proangiogenic cells.', 'The caspase-8 inhibitor zIETD abrogated the ex vivo formation of EPCs, inhibited EPC adhesion and migration, and reduced their capacity to improve neovascularization in vivo. Consistently, cells isolated from caspase-8-deficient mice exhibited a reduced capacity for enhancing neovascularization when transplanted into mice after hindlimb ischemia. Because inhibition of Caspase-8 reduced the adhesion and homing functions of EPCs, we further determined the surface expression of integrins and receptors involved in cell recruitment to ischemic tissues. Pharmacological inhibition of caspase-8 and genetic depletion of caspase-8 reduced the expression of the fibronectin receptor subunits alpha5 and beta1 and the SDF-1 receptor CXCR4. Moreover, we identified the E3 ubiquitin ligase Cbl-b, which negatively regulates integrin and receptor-mediated signaling, as a potential Caspase-8 substrate.']

['Exposure to air pollution is associated with increased cardiovascular morbidity, although the underlying mechanisms are unclear. Vascular dysfunction reduces arterial compliance and increases central arterial pressure and left ventricular after-load. We determined the effect of diesel exhaust exposure on arterial compliance using a validated non-invasive measure of arterial stiffness.', 'In a double-blind randomized fashion, 12 healthy volunteers were exposed to diesel exhaust (approximately 350 mug/m3) or filtered air for one hour during moderate exercise. Arterial stiffness was measured using applanation tonometry at the radial artery for pulse wave analysis (PWA), as well as at the femoral and carotid arteries for pulse wave velocity (PWV). PWA was performed 10, 20 and 30 min, and carotid-femoral PWV 40 min, post-exposure. Augmentation pressure (AP), augmentation index (AIx) and time to wave reflection (Tr) were calculated.', 'Blood pressure, AP and AIx were generally low reflecting compliant arteries. In comparison to filtered air, diesel exhaust exposure induced an increase in AP of 2.5 mmHg (p = 0.02) and in AIx of 7.8% (p = 0.01), along with a 16 ms reduction in Tr (p = 0.03), 10 minutes post-exposure.']

['Metastatic bone disease is one of the major causes of morbidity and mortality in prostate cancer patients. Bisphosphonates are currently used to inhibit bone resorption and reduce tumor-induced skeletal complications. More effective bisphosphonates would enhance their clinical value.', 'We tested several bisphosphonates in a green fluorescent protein (GFP)-expressing human prostate cancer nude mouse model. The in vivo effects of four bisphosphonates, including pamidronate, etidronic acid, and olpadronate, on bone tumor burden in mice intratibially inoculated with PC-3-GFP human prostate cancer cells were visualized by whole-body fluorescence imaging and X-ray.', 'The PC-3-GFP cells produced extensive bone lesions when injected into the tibia of immunocompromised mice. The skeletal progression of the PC-3-GFP cell growth was monitored by GFP fluorescence and the bone destruction was evaluated by X-ray. We showed that 3,3-dimethylaminopropane-1-hydroxy-1,1-diphosphonic acid (olpadronate) was the most effective bisphosphonate treatment in reducing tumor burden as assessed by GFP imaging and radiography. The GFP tumor area and X-ray score significantly correlated. Reduced tumor growth in the bone was accompanied by reduced serum calcium, parathyroid hormone-related protein, and osteoprotegerin.']

['Lumbar spinal manipulation (SM) is a popular, effective treatment for low back pain but the physiological mechanisms remain elusive. During SM, mechanoreceptors innervating the facet joint capsule (FJC) may receive a novel stimulus, contributing to the neurophysiological benefits of SM. The biomechanics of SM and physiological axial rotations were compared to determine whether speed or loading site affected FJC strain magnitudes or patterns.', 'Human lumbar spine specimens were tested during physiological rotations and simulated SM while measuring applied torque, vertebral motion, and FJC strain. During physiological rotations, specimens were actuated at T12 to 20 degrees left and right axial rotation at 2 degrees to 125 degrees per second. During SM simulations, a 7-mm impulse displacement was applied to L3, L4, or L5 at 5 to 50 mm per second.', 'Physiological rotations. Increasing displacement rate resulted in significantly larger torque magnitudes (P < .001), whereas vertebral kinematics and FJC strain magnitudes were unchanged (P > .05). Physiological rotations vs SM. Applied torque and vertebral rotation magnitudes were similar across speed and vertebral level. Total vertebral translations were slightly larger during physiological rotations vs SM at a given loading rate (P < .05). Patterns of vertebral motions and FJC strain during SM and physiological rotations varied significantly with loading rate (P < .05) but not with actuation site (P > .15).']

['Endothelial chimerism occurs in renal transplants, but factors involved in its development and its impact on outcome, are unknown. Most studies on chimerism are restricted to gender-mismatched combinations of female donor organs into male recipients. By using blood group antigen mismatches to detect chimeric cells, we circumvented this restriction. We determined which factors predispose for the development of endothelial chimerism, and how it influences graft survival.', "We studied 85 renal transplant biopsies of 24 patients with either blood group A or B, who received a blood group O kidney. Biopsies were scored according to BANFF '97. Blood group antigens were stained by immunohistochemistry. Semiquantitative scoring was performed by four independent observers.", 'Endothelial chimerism was found in 27/85 biopsies from 16/24 patients. All female recipients, but only half of the male recipients, had endothelial chimerism in their grafts (P < 0.025). In female recipients, endothelial chimerism occurred significantly earlier than in male recipients (P < 0.02). The presence of endothelial chimerism was not associated with: rejection, outcome, original renal disease, previous transplantations, age, warm/cold ischemia time, pretransplantation blood urea levels, or erythropoietin therapy.']

['Food habits, nutrient needs and intakes differ between males and females, although few nutritional studies on patients with coeliac disease (CD) have reported results stratified by gender.', 'To compare energy and nutrient intakes among 13-year olds diagnosed with CD in early childhood with those of a non-coeliac (NC) age- and gender-matched control group, and also with estimated average requirements (EAR).', 'A case-control study was conducted in Sweden 2006-2007 within the coeliac screening study ETICS (Exploring The Iceberg of Coeliacs in Sweden). Dietary intake was assessed among 37 adolescents (23 girls) diagnosed with CD at median age 1.7\xa0years (CD group) and 805 (430 girls) NC controls (NC group) using a food-frequency questionnaire covering 4\xa0weeks. Reported energy intake was validated by comparison with the calculated physical activity level (PAL).', 'Regardless of CD status, most adolescents reported an intake above EAR for most nutrients. However, both groups had a low intake of vitamin C, with 13% in the CD-group and 25% in the NC-group below EAR, and 21% of boys in the CD-group below EAR for thiamine. The intake of fatty acids was unbalanced, with a high intake of saturated and a low intake of unsaturated fats. Girls and boys in the CD-group had an overall lower nutrient density in reported food intake compared to girls and boys in the NC-group.']

['Folium Hibisci Mutabilis was one of the traditional Chinese medicines with pharmacological activities of wound healing, antibacterial and anti-inflammatory, normally applied to the clinical treatment of local purulent infection, scald, and epidemic parotitis. However, few people reported that its effects of extracts on RAW264.7, cells and TNF-α, IL-6, and NO levels in rats serum of inflammation rats.', 'We mainly adopted the RAW264.7, macrophage cell line which was intervened by lipopolysaccharide (L PS), to establish the model of inflammatory cells. The secretion changes of TNF, and IL-6, level in the model cell acted by the FHMAEs, were detected by ELISA, NO level changes were determined by nitrate reductase method; Arthritis model induced by Collagen Type II were chose, and regulatory role of FHMAEs on IL-6 and NO level in serum were observed, FHMAEs mechanism of action were investigated in the treatment of rheumatoid arthritis. The states of the model rats were recorded.', 'Release of TNF-α, IL-6, and NO in LPS-induced RAW264.7, cells were significantly inhibited and has a clear dose-response relationship; The TNF-α, IL-6 and NO levels were reduced by FHMAEs in experimental arthritis rats serum, and the status of rats were improved. At last, we found that IL-6, NO and TNF-α levels in the inflammatory cells could be reduced by FHMAEs greatly.']

['Oxidative stress has been advocated as a major cause for cardiovascular disease (CVD), and low plasma antioxidant concentrations are associated with endothelial dysfunction, the first step towards atherosclerosis. However, although the antioxidant content in fruits and vegetables may explain at least in part their protective effect against CVD, supplementation with antioxidant vitamins fails to improve endothelial function and reduce CVD risk. The aim of this study was to investigate the impact of a diet rich in antioxidants on endothelial function measured by flow-mediated dilatation (FMD) in volunteers at low cardiovascular risk.', 'In a crossover trial, 24 subjects (13 women, mean age 61\xa0±\xa03 years), received, in a randomised order, a 14-day high (HT) and a 14-day low (LT) antioxidant diets, with a 2-week wash-out (WO) in between. Both diets were comparable in daily portions of fruits and vegetables, and in alcohol, fibre and macronutrient intake, but differed in their total antioxidant capacity. Before and after each diet, anthropometrics, blood pressure, fasting plasma glucose, lipid profile, hepatic enzymes, circulating antioxidant concentrations, high sensitivity C-reactive protein (hs-CRP) and FMD were assessed. FMD increased significantly during the HT diet compared to the LT (p\xa0<\xa00.000). FMD values were 2.3% higher after HT compared with LT (p\xa0<\xa00.001) after adjustment for age, gender and diet order. α-tocopherol increased significantly (p\xa0<\xa00.05) and hs-CRP and of γ-glutamyltranspeptidase decreased significantly (p\xa0<\xa00.05 and p\xa0<\xa00.01, respectively) during the HT diet, compared with the LT diet.']

['We evaluated the endothelial and vascular smooth muscle function in patients with chronic severe anemia to determine whether increased basal nitric oxide levels contribute to the systemic vasodilation and high cardiac output seen in these patients.', 'Patients with chronic severe anemia have a high output state due to a low systemic vascular resistance. However, the cause of the low vascular resistance is unclear. Because hemoglobin is a potent inhibitor of endothelium-derived relaxing factor, we postulated that in chronic severe anemia, low circulating hemoglobin results in reduced inhibition of endothelium-derived relaxing factor. The basal endothelium-derived relaxing factor activity therefore increases, and this contributes significantly to the low systemic vascular resistance and the hyperdynamic state seen in this condition.', 'Hemodynamic variables and forearm blood flow (using plethysmography) were measured in eight patients with chronic severe anemia before (hematocrit 16 +/- 2% [mean +/- SD]) and within 24 h of red blood cell transfusion (n = 6, hematocrit 30 +/- 1%) and in six control subjects. The effect on baseline blood flow of blocking endothelium-derived relaxing factor activity with NG-monomethyl-L-arginine was investigated. In addition, the effects of both endothelium-dependent and endothelium-independent vasodilators on forearm blood flow were tested.', 'Baseline forearm blood flow was markedly increased in untreated patients (6.5 +/- 1.2 ml/min per 100 ml) compared with that in control subjects (2.8 +/- 0.7 ml/min per 100 ml, p < 0.0001, 95% confidence interval [CI] for difference -5 to -2.5). Red blood cell transfusion significantly reduced blood flow in the anemic patients to 3.5 +/- 1.1 ml/min per 100 ml (p < 0.001, 95% CI for difference -4.9 to -1.9), which was not significantly different from that in control subjects; increased systemic vascular resistance (796 +/- 141 to 1,230 +/- 151 dynes.s.cm-5, p < 0.001); and decreased cardiac output (4.9 +/- 0.6 to 3.5 +/- 0.5 liters/min per m2, p < 0.001). NG-monomethyl-L-arginine (16 mumol/min), a specific inhibitor of endothelium-derived relaxing factor, reduced forearm blood flow by an equal amount (p = 0.9, 95% CI for difference -0.7 to 0.8) in control subjects (0.98 +/- 0.39 ml/min) and treated patients (1.03 +/- 0.8 ml/min) but caused a threefold greater decrease in flow (2.9 +/- 0.9 ml/min) in untreated patients (p = 0.0003, 95% CI for difference between untreated patients and control subjects 1.1 to 2.7). These findings suggest increased basal endothelium-derived relaxing factor activity in patients with anemia. Stimulated forearm blood flows (both endothelium dependent and endothelium independent) were similar in all groups, confirming normal endothelial and smooth-muscle function.']

['Dental plaque has been suggested as a permanent reservoir of Helicobacter pylori (H. pylori) and a potential source of reinfection. The aims of this study were to investigate the presence of H. pylori in both dental plaque and the stomach and to evaluate the therapeutic effect of triple therapy on H. pylori in dental plaque.', 'Dental plaque and gastric biopsy samples were obtained from 65 patients with dyspeptic symptoms for endoscopic examination. The prevalence of H. pylori in dental plaque and stomach was determined with rapid urease test, histologic examinations and polymerase chain reaction assay based on the primer pair derived from the cagA gene of H. pylori. Triple therapy was administered to patients infected with H. pylori. H. pylori status was re-evaluated after eradication therapy.', 'Prior to treatment, H. pylori was found in the stomach in 38 of 65 (58%) patients and in dental plaque in 28 of 65 (43%) patients. The coexisting infection rate of H. pylori in both stomach and dental plaque was 74%. After triple therapy, H. pylori was eradicated from the stomach in 32 of 38 (84%) patients, but only 2 of 28 (7%) patients with coexisting H. pylori infections of stomach and dental plaque showed the elimination of H. pylori from dental plaque.']

['To construct a eukaryotic expression vector containing human cannabinoid receptor 2 (hCB2R) gene and investigate its expression, location and the influence on the apoptosis of cervical cancer Caski cells.', 'The eukaryotic expression vector GV230-hCB2R was constructed and identified by double enzyme digestion and DNA sequencing analysis. Then it was transfected into HEK293 cells and Caski cells by Lipofectamine(TM) 2000. The expression and cellular localization of hCB2R protein were detected by Western blotting and immunofluorescent cytochemistry combined with laser scanning confocal microscopy, the apoptosis rate was tested by flow cytometry. The mRNA and protein expressions of hCB2R, Bcl-2, Bax and Bad were examined by real-time fluorescent quantitative PCR (qRT-PCR) and Western blotting, respectively.', 'The gene fragment of 1128 bp was obtained by double enzyme digestion, it had 99% homology with human hCB2R gene nucleic acid sequence reported (NM_001841.2). After transfected into HEK293 cells, hCB2R protein, with the relative molecular mass (Mr) being 40 000, was expressed in both cytoplasm and cellular membrane. The over-expression of hCB2R promoted apoptosis of Caski cells via up-regulating the Bax, Bad expressions and down-regulating the Bcl-2 expression.']

['To evaluate the impact of body mass index (BMI) on perioperative outcomes and radiation exposure for ultrasound (US)-guided percutaneous nephrolithotomy (PCNL).', 'Data were prospectively collected for consecutive patients who underwent PCNL at the University of California, San Francisco, from July 2013 to November 2015. Patients were divided into 3 groups according to their BMI:\u2009<25 (normal weight), 25-29.9 (overweight), and >30 (obese) kg/m', 'One hundred thirty-five patients were enrolled; 93 cases were performed under US and 42 under fluoroscopic guidance. US successfully guided renal access in 76.9% of normal weight, 79.0% of overweight, and 45.7% of obese patients (P\u2009<\u2009.05). Mean fluoroscopic screening time and radiation exposure dose were reduced for US compared to fluoroscopy cases across all BMI categories (P\u2009<\u2009.05). As BMI increased, radiation exposure dose rose disproportionately faster compared to screening time (P\u2009<\u2009.001). No significant differences among the BMI groups were found with regard to complication rate, hospital stay, and stone-free status.']

['TAZ (Transcriptional co-Activator with PDZ-binding motif), is a biologically potent transcriptional coactivator and functions by binding to the PPXY motif present in several transcription factors. Notably, TAZ behaves as a transducer linking cytoplasmic signaling events to transcriptional regulation in the nucleus. Several different factors regulate TAZ expression and/or function. In particular, a major regulation of TAZ activity occurs through the Hippo pathway by a phosphorylation-mediated mechanism that causes its cytoplasmic sequestration or degradation.', 'Here we demonstrate that AMOTL2 robustly co-immunoprecipitates with TAZ, and their interaction is dependent on the WW domain of TAZ and the PPXY motif in the N-terminus of AMOTL2. Furthermore, we show that AMOTL2 colocalizes with TAZ in the cytoplasm of H441 human lung cells and regulates TAZ cytoplasm-to-nucleus translocation through direct protein-protein interaction. Interestingly, the overexpression of AMOTL2 inhibits the functional cooperation between the transcription factor TTF-1 and TAZ on the Surfactant C gene promoter, as well as the expression of other known target genes of these regulatory factors.']

['Although several kinds of evidence suggest that glycosaminoglycans (GAGs) and proteoglycans (PGs) may contribute to the development of beta2-microglobulin-related (Abeta2m) amyloidosis, the precise roles of these molecules for the development of Abeta2m amyloidosis are poorly understood.', 'We investigated the effects of GAGs and PGs on the depolymerization of Abeta2m amyloid fibrils at a neutral pH, as well as on the formation of the fibrils at an acidic pH in vitro, using fluorescence spectroscopy with thioflavin T and electron microscopy.', 'Depolymerization of Abeta2m amyloid fibrils at pH 7.5 at 37 degrees C was inhibited dose-dependently by the presence of some GAGs (heparin, dermatan sulfate, or heparan sulfate) or PGs (biglycan, decorin, or keratan sulfate proteoglycan). Electron microscopy revealed that a significant amount of Abeta2m amyloid fibrils remained in the reaction mixture with some lateral aggregation. Second, when monomeric beta2m was incubated with aggrecan, biglycan, decorin, or heparin at pH 2.5 at 37 degrees C for up to 21 days, the thioflavin T fluorescence increased depending on dose and time. Electron microscopy revealed the formation of rigid and straight fibrils similar to Abeta2m amyloid fibrils in beta2m incubated with biglycan for 21 days.']

['Oral tongue squamous cell carcinoma (OTSCC) is one of the most aggressive forms of head and neck/oral cancer (HNOC), and is a complex disease with extensive genetic and epigenetic defects, including microRNA deregulation. Identifying the deregulation of microRNA-mRNA regulatory modules (MRMs) is crucial for understanding the role of microRNA in OTSCC.', 'A comprehensive bioinformatics analysis was performed to identify MRMs in HNOC by examining the correlation among differentially expressed microRNA and mRNA profiling datasets and integrating with 12 different sequence-based microRNA target prediction algorithms. Confirmation experiments were performed to further assess the correlation among MRMs using OTSCC patient samples and HNOC cell lines. Functional analyses were performed to validate one of the identified MRMs: miR-21-15-Hydroxyprostaglandin Dehydrogenase (HPGD) regulatory module.', 'Our bioinformatics analysis revealed 53 MRMs that are deregulated in HNOC. Four high confidence MRMs were further defined by confirmation experiments using OTSCC patient samples and HNOC cell lines, including miR-21-HPGD regulatory module. HPGD is a known anti-tumorigenic effecter, and it regulates the tumorigenic actions of Prostaglandin E2 (PGE2) by converts PGE2 to its biologically inactive metabolite. Ectopic transfection of miR-21 reduced the expression of HPGD in OTSCC cell lines, and the direct targeting of the miR-21 to the HPGD mRNA was confirmed using a luciferase reporter gene assay. The PGE2-mediated upregulation of miR-21 was also confirmed which suggested the existence of a positive feed-forward loop that involves miR-21, HPGD and PGE2 in OTSCC cells that contribute to tumorigenesis.']

['Nuclear factor (NF)-kappaB is a key transcription factor that regulates inflammatory processes. In the present study, we assessed the hypothesis that blockade of NF-kappaB may ameliorate ventricular hypertrophy in response to chronic infusion of angiotensin II.', 'Mice with targeted disruption of the p50 subunit of NF-kappaB (KO) were used to block the activation of NF-kappaB. Male KO and age-matched wild-type (WT) mice were chronically infused with angiotensin II at the rate of 0.2 (low dose) or 2 microg/kg/min (high dose) for 4 weeks.', 'High- but not low-dose angiotensin II significantly increased systemic blood pressure and left ventricular weight in WT mice. In contrast, although the pressor response was slightly but significantly augmented, the hypertrophic effect of angiotensin II was significantly attenuated in KO mice. The attenuated hypertrophic responsiveness was confirmed histologically (cross-sectional area) and transcriptionally (atrial natriuretic peptide). Echocardiography revealed no evidence of cardiac dysfunction in angiotensin II-treated KO mice. Although phosphorylation of MAPKs, including ERK, JNK, or p38-MAPK, was not affected after 4 weeks of angiotensin II treatment in WT mice, phosphorylation of JNK was specifically abrogated in KO mice. Angiotensin II increased myocardial expression of proinflammatory cytokines and chemokines in WT mice, while expression of TNF-alpha and RANTES was paradoxically augmented in KO mice.']

['Mammalian target of rapamycin (mTOR) is a key kinase downstream of phosphoinositide 3-kinase (PI3K)/AKT predominantly involved in translational control in the presence of nutrients and energy. Despite the well known role of mTOR in carcinogenesis, its prognostic potential in lung cancer has not been investigated. Here, we quantitatively assessed mTOR protein expression in two large data sets to investigate the impact of mTOR expression on patient survival.', 'Automated quantitative analysis (AQUA), a fluorescent-based method for analysis of in situ protein expression, was used to assess mTOR expression in a training cohort of 167 lung cancer patients. An independent cohort of 235 lung cancer patients (from a second institution) was used for validation.', 'Tumors expressed mTOR in the cytoplasm in 56% and 50% of the cases in training and validation cohorts, respectively; mTOR expression was not associated with standard clinical or pathologic characteristics. Patients with high mTOR expression had a longer median overall survival compared with the low expressers (52.7 versus 38.5 months; log rank P = 0.06), which was more prominent in the adenocarcinoma group (55.7 versus 38.88 months; log rank P = 0.018). Multivariate analysis revealed an independent lower risk of death for adenocarcinoma and adenocarcinoma stage IA patients with mTOR-expressing tumors (hazard ratio, 0.48; 95% confidence interval, 0.24-0.98; P = 0.04, and hazard ratio, 0.12; 95% confidence interval, 0.03-0.72; P = 0.019, respectively).']

['Cultured fibroblasts of hypoxia-stimulated remodelled pulmonary artery (PA) adventitia proliferate at a greater rate compared with those of normal adventitia. Since protein kinase C (PKC) zeta is a replication repressor of normal adventitial fibroblasts, we hypothesized that loss of the repressor activity of PKCzeta might contribute to increased rate of proliferation in adventitial cells of remodelled PA.', 'Isolated PA adventitial fibroblasts of neonatal control (Fib-C) and chronic hypoxia-exposed (Fib-H) calves were used to test our hypothesis. For evaluation of the role of PKCzeta in hypoxia-induced vascular adventitial remodelling, expression and activation of PKCzeta were also examined in lung sections of Fib-C and Fib-H animals by immunoperoxidase staining. Although constitutively active PKCzeta expression attenuated DNA synthesis in Fib-C, it stimulated proliferation in Fib-H. PKCzeta-specific myristoylated pseudosubstrate peptide inhibitor (PKCzeta-PI) induced replication in Fib-C, whereas the inhibitor blocked DNA synthesis in Fib-H. Hypoxia stimulated PKCzeta as well as MAP kinase kinase (MEK)1/2 and extracellular signal-regulated kinase (ERK)1/2 phosphorylation in Fib-H cells. However, ERK1/2 activation was mediated by both MEK1/2-dependent and MEK1/2-independent PKCzeta-regulated mechanisms in hypoxia-exposed Fib-H. PKCzeta was selectively activated in the adventitial cells of the remodelled vascular wall, as demonstrated by strong immunoreactivity against the anti-phosphoPKCzeta antibody in the Fib-H lung sections.']

['The purpose of this study was to challenge current knowledge on the potential therapeutic advantages of stem cells in radiotherapy by developing an in vitro model of the healthy tissue surrounding or replacing the widely resected tumor. After radical surgery, the start of radiotherapy is often delayed due to wound healing process, with potential loss of the opportunity for treating microscopic disease instead of macroscopic early recurrence. Hyperfractionated radiotherapy, contrary to the standard one, can extend the limits of radical surgery and shorten the gap before the onset of postoperative radiotherapy, with potential improvement in local control.', 'By using both mesenchymal stem cells and pre-differentiated osteoblasts, cultured in proper pro-osteogenic media after cell irradiation, we investigated both the differences in the response to DNA damage between lineages undergoing differentiation in culture and the intensity of the mineralization process.', 'Ionizing radiation stimulated stem cell proliferation and differentiation at 0.5 Gy and 1 Gy, thus confirming in vitro the clinical results of hyperfractionated irradiation randomized trials in head and neck cancers -HNCs-.']

['To study the frequency of interstitial 7q deletions in B-cell lymphoproliferative disorders (B-LPDs).', 'Cases were collected from the clinical laboratory diagnosis database at USLabs/LabCorp over the past two years (2002 to 2004). Cases that showed deletions in the long arm of chromosome 7 were then reviewed. Interstitial deletions in the long arm of chromosome 7 were further investigated according to the indications for clinical laboratory studies and flow cytometry findings. The final clinical diagnosis for each case was obtained from the referring physician.', 'A total of 19,483 cases were included in this series. Eighty-five cases were observed to have either terminal or interstitial deletion in the long arm of chromosome 7. Of the 85 cases, 46 had interstitial deletions accounting for 54.1% of the 7q deletions combined. B-LPDs were found in 10 of the 46 cases, accounting for 21.7%. The B-LPDs associated with 7q interstitial deletions were diverse, including B-cell chronic lymphocytic leukemia (B-CLL) in five cases. The deleted region in the long arm of chromosome 7 in the 10 cases associated with B-LPDs was solely confined to the 7q22-q32 region.']

['Interleukin-8 (IL-8) is an important factor in the pathogenesis of psoriasis vulgaris, which is characterized by proliferation of keratinocytes, neutrophil infiltration and angiogenesis. Cysteine-rich 61 (Cyr61/CCN1), a secreted extracellular matrix protein, is a novel proinflammatory factor. Whether Cyr61 is involved in the development of psoriasis vulgaris via IL-8 production remains unknown. In this study we explore the role of Cyr61 in IL-8 expression regulation in vivo and in vitro.', 'Skin samples from normal donors and psoriasis vulgaris patients were examined the profile of Cyr61 and IL-8 using immunohistochemistry, real-time PCR and Western blotting. HaCaT cells were treated with Cyr61 and IL-8 expression was analyzed by real-time PCR and ELISA. Signal transduction pathways in Cyr61-induced IL-8 production were investigated by real-time PCR, western blotting, luciferase reporter assay or chromatin immunoprecipitation (ChIP) assay. IMQ-induced psoriasis-like mice were treated with anti-Cyr61monoclonal antibodies (mAb), or IgG1 as a control.', 'We found that Cyr61 was abundant in the epidermis of patients with psoriasis vulgaris and positively correlated with the pathogenesis of skin lesions. Cyr61 induced IL-8 production by keratinocytes in a dose dependent manner. This IL-8 synthesis occurred in an IL-1β- and TNF-α- independent mode via PI3K, AKT and JNK activation, with binding of enhanced AP-1, C/EBPβ and NF-κB to sites located in the IL-8 promoter region. Treatment with anti-Cyr61 mAb led to reduction of MIP-2 level, decreased neutrophil infiltration, and attenuated inflammation in vivo.']

['In mammalian cells, the relevance of homologous recombination in radiation-induced double-strand break (DSB) repair is not yet well understood. In the present work, the role of recombination between homologous chromosomes and homology-directed repair of DSB were studied, using X-ray-induced chromosomal aberrations as an end-point.', 'Human-hamster hybrid cells containing one or two copies of human chromosome 8 were used. If recombination between homologous chromosomes plays a dominant role in DSB repair, it is expected that X-irradiation of cells with two copies of chromosome 8 would result in a lower frequency of aberrations involving this chromosome compared with cells with only one copy of chromosome 8. The aberrations involving human chromosome 8 were detected by fluorescence in situ hybridization (FISH). Furthermore, a comparison between the hamster cell line XR-C1 (defective in non-homologous repair), CHO-9 (the wild-type cells) and the cell line XR-C1#8 (in which the defect of XR-C1 is complemented by human chromosome 8) was made to determine, indirectly, the involvement of homology-directed recombination in DSB repair.', 'The observed frequencies of aberrations per human chromosome 8 were not significantly different between cells containing one or two copies of this chromosome. The frequency of chromatid-type aberrations was doubled in XR-C1 cells compared with CHO-9 and XR-C1#8 cells.']

['Intra-articular injection of local anesthetics (LAs) is a common procedure for therapeutic purposes. However, LAs have been found toxic to articular cartilage, and hyaluronan may attenuate this toxicity. In this study we investigated whether hyaluronan attenuated lidocaine-induced chondrotoxicity, and if so, to elucidate the underlying mechanisms.', 'Human chondrocyte cell line SW1353 and newly isolated murine chondrocytes were incubated in culture medium containing hyaluronan and/or lidocaine for 72 h. Cell viability was evaluated using MTT assay. Cell apoptosis was detected with DAPI staining, caspase 3/7 activity assay and flow cytometry. Cell cycle distributions, ROS levels and mitochondrial membrane potential (ΔΨm) were determined using flow cytometry. The expression of p53 and p53-regulated gene products was measured with Western blotting.', 'Lidocaine (0.005%-0.03%) dose-dependently decreased the viability of SW1353 cells. This local anesthetic (0.015%, 0.025%) induced apoptosis, G2/M phase arrest and loss of ΔΨm, and markedly increased ROS production in SW1353 cells. Hyaluronan (50-800 μg/mL) alone did not affect the cell viability, but co-treatment with hyaluronan (200 μg/mL) significantly attenuated lidocaine-induced apoptosis and other abnormalities in SW1353 cells. Furthermore, co-treatment with lidocaine and hyaluronan significantly decreased the levels of p53 and its transcription targets Bax and p21 in SW1353 cells, although treatment with lidocaine alone did not significantly change these proteins. Similar results were obtained in ex vivo cultured murine chondrocytes.']

['Chronic airway eosinophil accumulation is characteristic of asthma. However, it remains unclear whether airway eosinophils enhance or reduce release of chemical mediators and/or action of the released mediators in the airways in vivo, because previous investigators have indicated that eosinophil-derived factors such as histaminase and arylsulfatase may alter the allergic reaction by metabolizing chemical mediators. Recently, we have developed a guinea pig model of propranolol-induced bronchoconstriction (PIB), which is mediated by lipid mediators such as thromboxane A2 (TxA2), cysteinyl leukotrienes (cLTs) and platelet activation factor (PAF). This study was conducted to explain the influence of airway eosinophil accumulation on antigen-induced bronchoconstriction and the following PIB, both of which are mediated by lipid mediators.', 'Guinea pigs were transnasally treated with 75 microg/kg of polymyxin-B or vehicle twice a week for a total of 3 weeks. Guinea pigs were anesthetized and treated with diphenhydramine hydrochloride, and then artificially ventilated 24 h after the last administration of polymyxin-B or vehicle followed by passive sensitization. Propranolol at a concentration of 10 mg/ml was inhaled 20 min after an aerosolized antigen challenge.', 'The proportion of eosinophils in bronchoalveolar lavage fluid obtained 15 min after the propranolol inhalation was significantly increased in guinea pigs treated with polymyxin-B compared with the vehicle. The polymyxin-B treatment did not affect antigen-induced bronchoconstriction or the following PIB.']

['The host response to infection by Plasmodium falciparum, the parasite most often responsible for severe malaria, ranges from asymptomatic parasitaemia to death. The clinical trajectory of malaria is influenced by host genetics and parasite load, but the factors determining why some infections produce uncomplicated malaria and some proceed to severe disease remain incompletely understood.', 'To identify molecular markers of severe falciparum malaria, human gene expression patterns were compared between children aged 6 months to 5 years with severe and uncomplicated malaria who were enrolled in a case-control study in Bandiagara, Mali. Microarrays were used to obtain expression data on severe cases and uncomplicated controls at the time of acute disease presentation (five uncomplicated and five severe), 1 week after presentation (three uncomplicated and three severe) and treatment initiation, and in the subsequent dry season (late convalescence, four uncomplicated and four severe). This is a pilot study for the first use of microarray technology in Mali.', 'Complement and toll-like receptor (TLR) pathways were differentially expressed, with severe cases showing higher expression of the C1q, TLR2, TLR4, TLR8, and CR1 genes. Other genes previously associated with malaria pathogenesis, GZMB, FOS and HSPA6, were also higher among severe cases. TLR2, TLR4, TLR8, CR1, GZMB, FOS, and HSPA6 genes were expressed at lower levels in severe cases at late convalescence.']

['As vascular surgeons strive to meet the Fistula First Initiative, some authors have observed a decrease in arteriovenous fistula (AVF) maturation rates in association with an increase in AVF creation. In May 2012, we adopted a practice change in an attempt to maintain the same high level of AVF creation while leading to a decrease in fistula failures.', 'A retrospective study was conducted of all dialysis access procedures performed by a single vascular surgeon before (period 1; before May 1, 2012) and after (period 2; after May 1, 2012) the change in practice pattern. The adopted change included favoring the brachiocephalic location unless the patient was an ideal anatomic candidate for a radiocephalic AVF, creating a larger and standardized arteriotomy, and using a large venous footplate whenever possible. The main outcome measure was primary functional patency at 1 year. Secondary outcome measures included primary patency at 1 year, time to maturation, type of fistula created, steal syndrome, and tunneled hemodialysis catheter infections.', 'Of 213 vascular access procedures performed, 191 (90%) were AVFs. There was no difference in use of AVFs between period 1 (93% AVFs) and period 2 (88% AVFs; P = .2). Use of brachiocephalic AVFs increased from 38% in period 1 to 56% in period 2 (P = .01), with a corresponding trend toward a decrease in radiocephalic AVFs in period 2 (36% in period 1 to 27% in period 2; P = .2). Primary functional patency at 1 year was 47% in period 1 and 63% in period 2 (P = .03). Primary patency at 1 year was 51% in period 1 and 70% in period 2 (P = .001). Time to reach functional maturation was decreased in period 2 (median, 76 vs 82.5 days; P = .046). There was no difference in steal syndrome (P = 1.0), and the incidence of hemodialysis catheter infections was lower in period 2 (0 vs 7 [7%]; P = .006).']

['A significant proportion of patients with connective tissue disease (CTD) have gastric esophageal reflux disease (GERD) symptoms despite receiving proton pump inhibitors (PPIs). Although pre-meal administration of PPIs is recommended in Western countries, the benefit of this administration timing in Japanese CTD patients with refractory GERD symptoms has not been proven.', 'To determine whether pre-dinner administration of PPIs is more efficacious for refractory GERD symptoms in Japanese CTD patients.', 'CTD patients receiving oral PPIs were instructed to take PPIs 1 h before dinner. Gastrointestinal symptoms were evaluated with frequency scale for the symptoms of GERD (FSSG) and gastrointestinal symptom rating scale (GSRS) before and after the intervention.', 'Pre-dinner administration of PPIs significantly improved FSSG total score, from a median of 8 to 6.5 (P = 0.005). Pre-dinner administration was more effective in patients with overt GERD symptoms (from median 18 to 10, P < 0.001) than in those with mild GERD symptoms (from median 2 to 2, P = 0.201). In addition to reflux syndrome, pre-dinner administration of PPIs significantly decreased abdominal pain syndrome and constipation syndrome of GSRS.']

['Pelvic floor exercises are invaluable for regaining continence but mechanisms are not fully understood. To contribute to the understanding of these mechanisms we investigated the contraction sequence of superficial vs deep pelvic floor muscles in 6 positions in continent and incontinent women.', 'The onset of contraction of the superficial and deep pelvic floor muscles was recorded by perineal and intravaginal surface electromyography in 32 continent and 50 incontinent women. The agreement between perineal and intravaginal recordings was calculated with the kappa statistic and the percent of agreement. Differences in onset between superficial and deep pelvic floor muscle contractions are reported as the median and IQR.', 'Perineal and intravaginal electromyography recordings used to define the onset of muscle activity showed a high level of agreement. In the continent group the superficial muscles almost always contracted before the deep muscles in all 6 positions. In the incontinent group the reverse sequence was observed in 3 of 6 positions. Higher and less consistent time differences in the onset of contraction of the 2 muscle layers were found in incontinent vs continent women.']

['The capacity of older adults to make healthcare decisions is often impaired in dementia and has been linked to performance on specific neuropsychological tasks. Within-person across-test neuropsychological performance variability has been shown to predict future dementia. This study examined the relationship of within-person across-test neuropsychological performance variability to a current construct of treatment decision (consent) capacity.', "Participants completed a neuropsychological test battery and a standardized capacity assessment. Standard scores were used to compute mean neuropsychological performance and within-person across-test variability. Assessments were performed in the participant's preferred location (e.g., outpatient clinic office, senior center, or home). Participants were recruited from the community with fliers and advertisements and consisted of men (N\xa0= 79) and women (N\xa0= 80) with (N\xa0= 83) or without (N\xa0= 76) significant cognitive impairment. Participants completed the MacArthur Competence Assessment Tool-Treatment and 11 neuropsychological tests commonly used in the cognitive assessment of older individuals.", 'Neuropsychological performance and within-person variability were independently associated with continuous and dichotomous measures of capacity, and within-person neuropsychological variability was significantly associated with within-person decisional ability variability. Prevalence of incapacity was greater than expected in participants with and without significant cognitive impairment when decisional abilities were considered separately.']

['Although the relation between day-to-day temperature change and coronary heart disease (CHD) mortality is well established, it is unknown whether temperature variation within 1 day, ie, diurnal temperature range (DTR), is an independent risk factor for acute CHD death.', 'We used time-series and case-crossover approaches to assess the relation between DTR and daily CHD mortality between 2001 and 2004 in Shanghai, China. Specifically, we used exposures averaged over periods varying from 1 to 5 days to assess the effects of DTR on CHD mortality. We estimated the percent increase in the number of daily deaths related to CHD that were associated with DTR, after adjustment for daily meteorologic conditions (temperature and relative humidity) and levels of outdoor air pollutants.', 'Both time-series and case-crossover analyses showed that DTR was significantly associated with the number of daily deaths related to CHD. A 1 degrees C increase in 2-day lagged DTR corresponded to a 2.46% (95% CI, 1.76% to 3.16%) increase in CHD mortality on time-series analysis, a 3.21% (95% CI, 2.23% to 4.19%) increase on unidirectional case-crossover analysis, and a 2.13% (95% CI, 1.04% to 3.22%) increase on bidirectional case-crossover analysis.']

['Data on the prognostic significance of promoter CpG island methylation in colorectal cancer (CRC) are conflicting, possibly due to associations between methylation and other factors affecting survival such as genetic alterations and use of adjuvant therapy. Here, we examine the prognostic impact of promoter methylation in patients with CRC treated with surgery alone in the context of microsatellite instability (MSI), BRAF and KRAS mutations.', 'One hundred and seventy-three CRCs were analyzed for promoter methylation of 19 tumor suppressor and DNA repair genes, the CpG island methylator phenotype (CIMP), MSI, the exon 15 V600E BRAF mutation and KRAS codon 12 and 13 mutations.', 'Unsupervised hierarchical clustering based on methylation status of 19 genes revealed three subgroups: cluster 1 [CL1, 57% (98/173) of CRCs], cluster 2 [CL2, 25% (43/173) of CRCs], and cluster 3 [CL3, 18% (32/173) of CRCs]. CL3 had the highest methylation index (0.25, 0.49, and 0.69, respectively, P = <0.01) and was strongly associated with CIMP (P < 0.01). Subgroup analysis for tumor stage, MSI, and BRAF status showed no statistically significant differences in survival between CL1, CL2, and CL3 nor between CIMP and non-CIMP CRCs. Analyzing genes separately revealed that CHFR promoter methylation was associated with a poor prognosis in stage II, microsatellite stability (MSS), BRAF wild-type (WT) CRCs: multivariate Cox proportional HR = 3.89 [95% confidence interval (CI), 1.58-9.60, P < 0.01; n = 66] and HR = 2.11 (95% CI, 0.95-4.69, P = 0.068, n = 136) in a second independent population-based study.']

['Stress and conditioned responses to drug cues have been implicated as critical factors in relapse to drug use. In the animal literature, both the conditioned effects of drug-related stimuli and the unconditioned effects of foot-shock stress have been well documented to reinstate extinguished drug-seeking behavior. What has remained largely unexplored, however, is the significance of stimuli conditioned to foot-shock stress for the resumption of drug seeking. Additionally, although relapse is often the result of several risk factors acting in combination, the possibility that interactions among risk factors such as conditioned stress and drug cues may intensify drug-seeking behavior has received little experimental attention.', 'The purpose of this study was to examine the individual and interactive effects of a stimulus conditioned to foot-shock stress (STRESS CS) and a stimulus conditioned to ethanol reward (EtOH CS) on the reinstatement of ethanol-seeking behavior following extinction.', 'Male Wistar rats were trained to orally self-administer 10% ethanol on a fixed-ratio 3 schedule of reinforcement. The EtOH CS was established by response-contingently pairing 0.5 s illumination of a white cue light with each reinforced response. The STRESS CS was established by pairing a continuous white noise (70 dB) with intermittent foot shock (10 min; 0.5 mA; 0.5 s on; mean off period of 40 s). Ethanol dependence was induced by an ethanol vapor-inhalation procedure. After ethanol-maintained instrumental responding was extinguished by withholding ethanol and the EtOH CS, reinstatement tests were conducted.', 'Both exposure to the STRESS CS and response-contingent presentation of the EtOH CS reinstated extinguished responding at the previously active, ethanol-paired lever without further ethanol availability. When response-contingent availability of the EtOH CS was preceded by exposure to the STRESS CS, interactive effects of these stimuli on responding were observed. However, both the individual and interactive effects of the STRESS CS and the EtOH CS reached statistical significance only in rats with a history of ethanol dependence but not in ethanol-nondependent rats.']

['Hip fracture patients experience high pain levels during postoperative rehabilitation. The role of surgical technique on postoperative pain has not been evaluated previously.', 'One hundred and seventeen hip fracture patients were included in a descriptive prospective study. All patients received continuous epidural analgesia and were treated according to a standardized perioperative rehabilitation programme. Resting pain, pain on hip flexion, and walking were measured during daily physiotherapy sessions on a verbal five-point rating scale during the first four postoperative days. Patients were stratified into four groups according to surgical procedure: screws or pins, arthroplasty, dynamic hip screw (DHS), and intra-medullary hip screw (IMHS).', 'Cumulated pain levels were significantly different between surgical procedures both for hip flexion (P=0.002) and for walking (P=0.02) with highest dynamic pain levels for patients who had either DHSs or IMHSs compared with arthroplasty or parallel implants. There were significant negative correlations between ambulatory capacity assessed by the cumulated ambulation score and both the dynamic cumulated pain scores on hip flexion (r=-0.43, P<0.001) and walking (r=-0.36, P=0.004).']

["The consequences of high radiation dose for patient and staff demand constant improvements in X-ray dose reduction technology. This study assessed non-inferiority of image quality and quantified patient dose reduction in interventional cardiology for an anatomy-specific optimised cine acquisition chain combined with advanced real-time image noise reduction algorithms referred to as 'study cine', compared with conventional angiography.", 'Fifty patients underwent two coronary angiographic acquisitions: one with advanced image processing and optimised exposure system settings to enable dose reduction (study cine) and one with standard image processing and exposure settings (reference cine). The image sets of 39 patients (18 females, 21 males) were rated by six experienced independent reviewers, blinded to the patient and image characteristics. The image pairs were randomly presented. Overall 85\u2009% of the study cine images were rated as better or equal quality compared with the reference cine (95\u2009% CI 0.81-0.90). The median dose area product per frame decreased from 55 to 26\xa0mGy.cm(2)/frame (53\u2009% reduction, p\u2009<\u20090.001).']

['Current methods of mesenchymal stromal cell (MSC) cryopreservation result in variable post-thaw recovery and phenotypic changes caused by freezing. The objective of this investigation was to determine the influence of ex\xa0vivo cell expansion on phenotype of MSCs and the response of resulting phenotypes to freezing and thawing.', 'Human bone marrow aspirate was used. MSCs were isolated and cells were assessed for total count, viability, apoptosis and senescence over 6 passages (8-10 doublings/passage) in ex vivo culture. One half of cells harvested at each passage were re-plated for continued culture and the other half were frozen at 1°C/min in a controlled-rate freezer. Frozen samples were stored in liquid nitrogen, thawed and reassessed for total cell count, viability and senescence immediately and 48 h after thaw.', 'Viability did not differ significantly between samples before freeze or after thaw. Senescence increased over time in pre-freeze culture and was significantly higher in one sample that had growth arrest both before freeze and after thaw. Freezing resulted in similar initial post-thaw recovery in all samples, but 48-h post-thaw growth arrest was observed in the sample with high senescence only.']

['Recent advances in post-cardiac arrest (CA) care including therapeutic hypothermia (TH) have improved survival and favorable neurologic outcomes for survivors of CA. Survivors often present with deep coma and lack of brainstem reflexes, which are generally associated with adverse outcomes in many disease processes. Little is known regarding the role of initial emergency department (ED) neurological examination and its potential for prognostication.', 'The purpose of this study is to determine if components of a standardized neurologic examination are reliable prognosticators in patients recently resuscitated from CA. We hypothesize that lack of neurologic function does not reliably predict an adverse outcome and, therefore, should not be used to determine eligibility for TH.', 'A standardized neurologic examination was performed in the ED on a prospective, convenience cohort of post-CA patients presenting to a CA resuscitation center who would undergo a comprehensive postarrest care pathway that included TH. Data such as prior sedation or active neuromuscular blockade were documented to evaluate for the presence of possible confounders. Examination findings were then compared with hospital survival and neurologic outcome at discharge as defined by the cerebral performance category (CPC) score as documented in the institutional TH registry.', 'Forty-nine subjects were enrolled, most of whom presented comatose with a Glasgow Coma Scale of 3 (n=41, 83.7%). Nineteen subjects (38.8%) had absence of all examination findings, of which 4 of 19 (21.1%) survived to hospital discharge. Of those with at least 1 positive examination finding, 13 of 30 subjects (43.3%) survived to hospital discharge. Subgroup analysis showed that 9 of the 19 patients with absence of brainstem reflexes did not have evidence of active neuromuscular blockade at the time of the examination; 2 of 9 (22.1%) survived to hospital discharge. Eight of these subjects in this group had not received any prior sedation; 1 of 8 (12.5%) survived to hospital discharge. Only 1 of the 17 subjects who survived was discharged with poor neurologic function with a CPC score=3, whereas all others who survived had good neurologic function, CPC score=1.']

['This study sought to assess in patients undergoing transcatheter aortic valve implantation (TAVI), the prevalence and impact of incomplete coronary revascularization defined as >50% coronary artery or graft diameter stenosis on visual assessment of the coronary angiogram.', 'TAVI is an established treatment option in elderly patients with aortic stenosis (AS) and a (very) high operative risk. Coronary artery disease (CAD) is often associated with AS.', 'A single-center cohort of consecutive patients undergoing TAVI between November 2005 and June 2012 was evaluated for the presence of significant CAD. The decision to revascularize and pursue complete revascularization was made by heart team consensus.', 'A total of 263 consecutive patients with a mean age of 80 ± 7 years and 51% male underwent TAVI with a median follow-up duration of 16 months (interquartile range: 4.2 to 28.1\xa0months). Significant CAD with myocardium at risk was present in 124 patients (47%), 44 of whom had had previous coronary artery bypass grafting (CABG), and the median SYNTAX score in the 81\xa0patients without previous CABG was 9.00 (2.38 to 15.63). Staged percutaneous coronary intervention (PCI) was planned in 19 (15%) and concomitant PCI with TAVI in 20 (16%). The median post-procedural residual SYNTAX score of patients without prior CABG was 5.00 (0.13 to 9.88). Overall, 99 patients (37%) (61 with no CABG and 38 CABG patients) had incomplete revascularization after\xa0TAVI. Revascularization status did not affect clinical endpoints. Kaplan-Meier survival curves for patients with and without complete revascularization demonstrated a 1-year mortality of 79.9% versus 77.4% (p\xa0= 0.85), respectively.']

['Bronchial smooth muscle (BSM) cells from asthmatic patients maintain in vitro a distinct hyper-reactive ("primed") phenotype, characterized by increased release of pro-inflammatory factors and mediators, as well as hyperplasia and/or hypertrophy. This "primed" phenotype helps to understand pathogenesis of asthma, as changes in BSM function are essential for manifestation of allergic and inflammatory responses and airway wall remodelling.', 'To identify signalling pathways in cultured primary BSMs of asthma patients and non-asthmatic subjects by genome wide profiling of differentially expressed mRNAs and activated intracellular signalling pathways (ISPs).', 'Transcriptome profiling by cap-analysis-of-gene-expression (CAGE), which permits selection of preferentially capped mRNAs most likely to be translated into proteins, was performed in human BSM cells from asthmatic (n=8) and non-asthmatic (n=6) subjects and OncoFinder tool were then exploited for identification of ISP deregulations.', 'CAGE revealed >600 RNAs differentially expressed in asthma vs control cells (p≤0.005), with asthma samples showing a high degree of similarity among them. Comprehensive ISP activation analysis revealed that among 269 pathways analysed, 145 (p<0.05) or 103 (p<0.01) are differentially active in asthma, with profiles that clearly characterize BSM cells of asthmatic individuals. Notably, we identified 7 clusters of coherently acting pathways functionally related to the disease, with ISPs down-regulated in asthma mostly targeting cell death-promoting pathways and up-regulated ones affecting cell growth and proliferation, inflammatory response, control of smooth muscle contraction and hypoxia-related signalization.']

['To investigate the protective effect and the possible mechanism of curcumin on anti-atherosclerosis.', 'Morphological changes of atherosclerotic lesions taken from apoE knockout (apoE-/-) mice were determined by hematoxylin- eosin staining. Intracellular lipid droplets and lipid levels were assayed by oil red O staining and HPLC. The protein expression of caveolin-1 was quantified by Western blotting. Translocation and the expression of sterol response element-binding protein-1 (SREBP-1) were indirectly detected by an immunofluorescence analysis.', 'The administration of 20 mg. kg(-1 ). d(-1 )curcumin to apoE-/- mice for 4 months induced a 50% reduction of atherosclerotic lesions and yielded a 5- fold increase in the caveolin-1 expression level as compared to the model group. Rat vascular smooth muscle cells (VSMC) pretreated with 50 mg/L ox-lipid density lipoprotein(ox-LDL) for 48 h increased cellular lipid contents, and stimulated SREBP-1 translocation, but decreased the caveolin-1 expression level. Lipid-loaded cells exposed to curcumin at various concentrations (12.5, 25, and 50 micromol/L) for different durations (0, 6, 12, 24, and 48 h) significantly diminished the number and area of cellular lipid droplets, total cholesterol, cholesterol ester, and free cholesterol accompanying the elevation of the caveolin-1 expression level (approximately 3-fold); the translocation of SREBP-1 from the cytoplasm to the nucleus was inhibited compared with the models. Lipid-loaded VSMC exposed to N-acetyl- Leu-Leu-norleucinal, a SREBP-1 protease inhibitor, showed increased nuclear translocation of SREBP-1, reduced caveolin-1 expression level, and upregulated cellular lipid levels.']

['Glycosylated hemoglobin (HbA1c) is commonly used to assess long-term blood glucose control in patients with diabetes mellitus. Numerous conditions including hemoglobinopathies can alter HbA1c measurements and cause misleading results.', 'To report a 13-year-old male with Type 1 diabetes mellitus who had low HbA1c measurements, despite persistent hyperglycemia.', 'HbA1c was initially measured by immunoassay. Hb electrophoresis was then employed to assess potential Hb variants. Electrospray ionization (ESI) tandem mass spectrometry of isolated Hb and gene sequencing of the Hbβ gene were used to specifically identify the Hb variant.', "HbA1c measurement by immunoassay revealed an unusually low HbA1c of 3.9%. Hb electrophoresis revealed an aberrant Hb. The ESI mass spectrum of the intact Hb sample revealed a variant β-chain of 15,881 Da, 14 Da heavier than the mass of the normal Hb β-chain (15,867 Da). Sequence analysis of the 965.45 Da peptide suggested a substitution of valine (Val) to acetylated alanine (Ala). The DNA sequence of the patient's Hbβ gene revealed a single-base heterozygous mutation (GTG to GCG) at Base 2 of the codon of the first amino acid, producing a Val→Ala substitution, previously termed Hb-Raleigh. Because the acetylated N-terminal amino acid of the Hb-Raleigh β chain cannot be glycated, the HbA1c immunoassay will result in falsely low HbA1c levels."]