Datasets:

HariModelMaven
/

pumed-finetuning

Dataset card Data Studio Files Files and versions Community

Split (3)

train · 8k rows

instruction stringlengths 22 321	context stringlengths 75 3.6k	context_neg stringlengths 75 3.6k
Does brain-derived neurotrophic factor augment peristalsis by augmenting 5-HT and calcitonin gene-related peptide release?	Brain-derived neurotrophic factor (BDNF) acts rapidly to modulate synaptic neurotransmission in the brain. Although present in neurons, glial cells, and mucosal cells of the colon, and in higher concentrations than in brain, the action of BDNF in gut have not been characterized. The aim of this study was to identify the role of BDNF in mediating the peristaltic reflex. BDNF and a specific antiserum were examined for their effects on the peristaltic reflex and release of the sensory mediators serotonin and calcitonin gene-related peptide in rat colon. The peristaltic reflex and release of serotonin and calcitonin gene-related peptide were also examined in genetically modified mice (BDNF(+/-)) with reduced levels of BDNF. Endogenous brain-derived neurotrophic factor was released into the sensory compartment in a stimulus-dependent manner during the peristaltic reflex induced by mucosal stimulation but not muscle stretch. BDNF stimulated and immunoneutralization of endogenous BDNF reduced ascending contraction and descending relaxation of circular muscle and release of serotonin and calcitonin gene-related peptide during the peristaltic reflex induced by mucosal stimulation but not muscle stretch. The peristaltic reflex and release of serotonin and calcitonin gene-related peptide during the peristaltic reflex induced by mucosal stimulation but not muscle stretch were significantly reduced in BDNF(+/-) mice.	The pre-treatment presence of at least six efferent patent vessels (EPV) from the AAA sac and/or AAA thrombus volume ratio (VR%) <40% are considered to be positive predictive factors for persistent type II endoleak (ELIIp). The aim of the present study was to evaluate the effectiveness of sac embolization during EVAR in patients with pre-operative morphological risk factors (p-MRF) for ELIIp. Patients undergoing EVAR and intra-procedural AAA sac embolization (Group A, 2012-2013) were retrospectively selected and compared with a control group of patients with the same p-MRF, who underwent EVAR without intra-procedural sac embolization (Group B, 2008-2010). The presence of ELIIp was evaluated by duplex ultrasound at 0 and 6 months, and by contrast enhanced ultrasound at 12 months. The association between AAA diameter, age, COPD, smoking, anticoagulant therapy, and AAA sac embolization with ELIIp was evaluated using multiple logistic regression. The primary endpoint was the effectiveness of the intra-procedural AAA sac embolization for ELIIp prevention. Secondary endpoints were AAA sac evolution and freedom from ELIIp and embolization related re-interventions at 6-12 months. Seventy patients were analyzed: 26 Group A and 44 Group B; the groups were homogeneous for clinical/morphological characteristics. In Group A the median number of coils positioned in AAA sac was 4.1 (IQR 1). There were no complications related to the embolization procedures. A significantly lower number of ELIIp was detected in Group A than in Group B (8/26 vs. 33/44, respectively, p < .001) at discharge, and this was confirmed at 6-12 months (7/26 vs. 30/44 respectively, p = .001, and 5/25 vs. 32/44, respectively, p < .001). On multivariate analysis, intra-procedural AAA sac embolization was the only factor independently associated with freedom from ELIIp at 6 (OR 0.196, 95% CI 0.06-0.63; p = .007) and 12 months (OR 0.098, 95% CI 0.02-0.35; p < .001). No differences in median AAA sac diameter shrinkage were detected between the two groups at 6-12 months (p = .42 and p = .58, respectively). Freedom from ELIIp related and embolization related re-interventions was 100% in both groups, at 6 and 12 months.
Does a tissue-specific protein purification approach in Caenorhabditis elegans identify novel interaction partners of DLG-1/Discs large?	Affinity purification followed by mass spectrometry (AP/MS) is a widely used approach to identify protein interactions and complexes. In multicellular organisms, the accurate identification of protein complexes by AP/MS is complicated by the potential heterogeneity of complexes in different tissues. Here, we present an in vivo biotinylation-based approach for the tissue-specific purification of protein complexes from Caenorhabditis elegans. Tissue-specific biotinylation is achieved by the expression in select tissues of the bacterial biotin ligase BirA, which biotinylates proteins tagged with the Avi peptide. We generated N- and C-terminal tags combining GFP with the Avi peptide sequence, as well as four BirA driver lines expressing BirA ubiquitously and specifically in the seam and hyp7 epidermal cells, intestine, or neurons. We validated the ability of our approach to identify bona fide protein interactions by identifying the known LGL-1 interaction partners PAR-6 and PKC-3. Purification of the Discs large protein DLG-1 identified several candidate interaction partners, including the AAA-type ATPase ATAD-3 and the uncharacterized protein MAPH-1.1. We have identified the domains that mediate the DLG-1/ATAD-3 interaction, and show that this interaction contributes to C. elegans development. MAPH-1.1 co-purified specifically with DLG-1 purified from neurons, and shared limited homology with the microtubule-associated protein MAP1A, a known neuronal interaction partner of mammalian DLG4/PSD95. A CRISPR/Cas9-engineered GFP::MAPH-1.1 fusion was broadly expressed and co-localized with microtubules.	In patients undergoing total knee replacement (TKR), most blood loss occurs post-operatively, and the return of unwashed filtered shed blood (USB) from post-operative drainage may represent an alternative to allogeneic blood transfusion (ABT). We evaluated the impact of USB return on the cellular immune response (CIR) after TKR. Forty TKR patients, intended to receive post-operative USB, entered the study. Blood samples were obtained before and 6 h, 24 h, 72 h and 7 days after surgery, and from USB, after it had been passed through a 40-microm filter. Full blood cell counts, lymphocyte subsets and immunoglobulins (IgA, IgG, IgM) were measured in all samples. A set of clinical data was collected from each patient. Twenty-four of the 25 patients received a mean of 1.2 USB units and did not need additional ABT (USB group). Twelve of the 15 remaining patients who received neither USB nor ABT served as a control group for the post-operative CIR study. All patients showed a post-operative decrease in T-cell and natural killer (NK) cell counts, but not B-cell counts, and there were no significant differences between the groups with regard to CIR parameters, post-operative infection or hospital stay.
Do extended high-frequency ( 9-20 kHz ) audiometry reference thresholds in 645 healthy subjects?	The aim of the present study was to study patterns in the extended spectrum of the human hearing (0.125 to 20 kHz) in order to obtain reference thresholds. Then, we compare our values with existing results at extended high-frequencies (8 to 20 kHz) in an attempt to establish new standards for potential international adoption. A prospective study in a group of otologically healthy subjects. A total of 645 subjects aged between 5 and 90 years were recruited. Pure-tone thresholds were determined for conventional and extended high-frequencies. There was an increase in the hearing thresholds as a function of frequency and age. For the 20 to 69 years old group, thresholds were lower in females than in males, especially at 12.5 and 16 kHz. Our threshold values are comparable to those presented in previous studies that used different instrumentation and populations.	Bacterial infections and bacteremia in acute liver failure may at least partly be attributed to translocation of enteric bacteria. Attempts to prevent or treat such infections by the use of antibiotics may instead result in overgrowth of surviving microbes. In the present study, normal saline (1.5 ml/100 g body weight), phosphatidylcholine (1.5 ml/100 g body weight), and phosphatidylinositol (1.5 ml/100 g body weight) were orally administered by means of a gastric tube both 12 h and 30 min before operation. Effects of enteric administration of phospholipids on the prevention of enteric bacterial translocation, intestinal and mucosal mass, and enterocyte protein contents in acute liver failure induced by subtotal liver resection in the rat were evaluated. The incidence of bacterial translocation increased significantly 2 and 4 h after 90% hepatectomy as compared with sham-operated animals. Enteric administration of phospholipids, however, significantly reduced the incidence of bacterial translocation after 90% hepatectomy. Phospholipid treatment prevented the postoperative decrease in intestinal mucosal mass and enterocyte protein content.
Does mixing bone graft with OP-1 improve cup or stem fixation in revision surgery of the hip : 5-year follow-up of 10 acetabular and 11 femoral study cases and 40 control cases?	Bone morphogenetic proteins (BMPs) have the potential to improve incorporation of allograft bone in revision surgery. This could result in improved fixation and graft incorporation. We evaluated the effect of mixing OP-1 (BMP-7) with morselized allograft in hip revisions. In a case-control study, 20 acetabular revisions (10 in the study group, 10 controls) and 41 femoral revisions (11 in study group, 30 controls) were done using impaction allografting. The migration of the cups and stems was studied with radiostereometric analysis (RSA) for up to 5 years. Changes of bone mineral density around the femoral component were measured with dual energy X-ray adsorptiometry for 2 years. Bone remodeling and the extent of radiolucent lines were evaluated on conventional radiographs after 5 years. The clinical results were documented using Harris hip score. In the cup study, there was no significant difference in implant migration between the study and control groups. 4 sockets in the study group were classified as radiographically loose after 5 years and 2 of them were revised after 5 years. After 2 years, the stems in the study group showed slightly increased posterior tilt (0.3 degrees , p = 0.03). 1 stem in the study group loosened and was revised during the third year of observation.	To study the role of autonomic nervous innervation in the etiology of peptic ulcer, we investigated the blood pressure in patients with peptic ulcer. In 100,085 Japanese adults who were undergoing health screening examinations, including barium meal study, there were endoscopic evaluation-confirmed diagnoses of gastric ulcer in 769 cases and of duodenal ulcer in 344 cases. The blood pressure in those patients was compared with that in 57,208 normal Japanese controls with no gastrointestinal abnormalities, as confirmed by barium meal study. The blood pressure of younger and middle-aged men with gastric and duodenal ulcer were lower than those of normal control men. In women, except for the diastolic pressure of those in their 50s, the blood pressure in patients with peptic ulcer and normal controls did not differ significantly. The incidence of duodenal ulcer or of gastric ulcer in men was inversely related to the systolic and diastolic pressure. No definite relationship in this respect was seen in women.
Is aBCC4 required for cell proliferation and tumorigenesis in non-small cell lung cancer?	Multidrug resistance protein 4 (MRP4), also known as ATP-cassette binding protein 4 (ABCC4), is a member of the MRP/ABCC subfamily of ATP-binding cassette transporters, which are capable of pumping a wide variety of drugs out of the cell. However, little is known about the function of ABCC4 in the proliferation of lung cancer cells. ABCC4 mRNA and protein levels in lung cancer cell lines were measured by real-time polymerase chain reaction and Western blot, respectively. A lentivirus-mediated RNA interference technique was used to inhibit ABCC4 mRNA expression in A549 and 801D cells. The function of ABCC4 in cell growth was investigated by MTS and colony formation assays. The role of ABCC4 in cell cycle progression was evaluated by flow cytometry and Western blot analysis. ABCC4 mRNA levels in 30 pairs of tumors and corresponding matched adjacent normal tissues from non-small cell lung cancer patients were detected by real-time polymerase chain reaction. ABCC4 was highly expressed in lung cancer cell lines. ABCC4 expression was markedly downregulated in A549 and 801D cells using the RNA interference technique. Suppression of ABCC4 expression inhibited cell growth. The percentage of cells in G1 phase was increased when ABCC4 expression was suppressed. Phosphorylation of retinoblastoma protein was weakened, originating in the downregulation of ABCC4. ABCC4 mRNA was highly expressed in lung cancer tissue and lung cancer cell lines.	The association between electrocardiographic (ECG) abnormalities and deaths from cardiovascular diseases (CVD) and ischemic heart disease (IHD) has been reported in the general population, but there is little information regarding persons with type 2 diabetes. Minor and major ECG abnormalities were identified and classified according to the Minnesota Code in a longitudinal study of 1605 Pima Indians aged > or =35 years with type 2 diabetes. Underlying causes of death were determined by review of all available clinical records, autopsy reports, medical examiners' findings, and death certificates. During a median follow-up of 14.1 years (range 0.1 to 33.8 years), there were 190 CVD deaths, 135 (71.1%) of which were attributable to IHD. The age-adjusted CVD death rates in men with none, minor, and major ischemic ECG abnormalities were 7.3, 12.2 and 27.8, and in women, 4.3, 4.8 and 12.5 per 1000 person-years, respectively. After adjustment for other co-variables in a multiple proportional hazards model, subjects with minor and major ischemic abnormalities on ECG had 1.22 (95% CI, 0.76-1.97) and 1.83 (95% CI, 1.21-2.76) times the CVD death rate, and 1.32 (95% CI, 0.70-2.50) and 2.12 (95% CI, 1.26-3.57) times the IHD death rate of those with no ischemic ECG abnormalities, respectively.
Is color vision but not visual attention altered in migraine?	To examine visual search performance in migraine and headache-free control groups and to determine whether reports of selective color vision deficits in migraine occur preattentively. Visual search is a classic technique to measure certain components of visual attention. The technique can be manipulated to measure both preattentive (automatic) and attentive processes. Here, visual search for colored targets was employed to extend earlier reports that the detection or discrimination of colors selective for the short-wavelength sensitive cone photoreceptors in the retina (S or "blue" cones) is impaired in migraine. Visual search performance for small and large color differences was measured in 34 migraine and 34 control participants. Small and large color differences were included to assess attentive and preattentive processing, respectively. In separate conditions, colored stimuli were chosen that would be detected selectively by either the S-, or by the long- (L or "red") and middle (M or "green")-wavelength sensitive cone photoreceptors. The results showed no preattentive differences between the migraine and control groups. For active, or attentive, search, differences between the migraine and control groups occurred for colors detected by the S-cones only, there were no differences for colors detected by the L- and M-cones. The migraine group responded significantly more slowly than the control group for the S-cone colors.	During sepsis, a two- to four-fold increase in circulating growth hormone (GH) is seen with 40-50% reductions in plasma insulin-like growth factor (IGF)-I. The suppressors of cytokine signaling (SOCS), inhibitors of cytokine, and growth factor signaling via the janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway have been implicated in the development of hepatic GH resistance. In this study we examine the effects of sepsis on GH-induced IGF-I expression and potential mechanisms for GH resistance. Prospective experimental study. University research laboratory. Male Sprague-Dawley rats. Rats were randomized to laparotomy alone (control) or implantation of fecal agar pellets inoculated with Escherichia coli and Bacteroides fragilis (sepsis). GH was injected intravenously to assess hepatic IGF-I synthesis and GH signaling. Plasma IGF-I was measured in both groups at baseline (4 hrs postoperatively) and then again at 12 hrs and 24 hrs after GH administration. Basal IGF-I levels were similar in both groups, but controls had a 35% increase in IGF-I at 12 hrs, whereas septic rats demonstrated reductions in circulating IGF-I at 12 and 24 hrs after GH. Hepatic expression of SOCS-1, -2, -3, and cytokine-inducible SH2-containing protein (CIS) were determined at 1, 4, 8, and 24 hrs in septic and control rats by Northern blot. SOCS-1, SOCS-3, and CIS messenger RNA in liver were increased from 4 to 8 hrs after the induction of sepsis (p < .05 for SOCS-1 and -3). Total GH receptor (GHR), JAK2, and STAT5 signaling proteins and the time course of STAT5 activation were also measured in liver after recombinant human GH administration by immunoblot and electrophoretic mobility shift analysis. Levels of total GHR, JAK2, and STAT5 were unaltered in liver from septic rats. However, phosphorylated STAT5 and STAT5 DNA binding were significantly reduced 30 mins after GH administration in liver from septic rats.
Is there no transmural heterogeneity in an index of action potential duration in the canine left ventricle?	Transmural heterogeneity in ventricular repolarization demonstrated in vitro has been difficult to confirm in vivo. Whether this discrepancy reflects a physiological phenomenon or a methodological problem remains a vivid matter of debate despite a plethora of experimental work. Therefore, we have measured the relevant electrophysiological parameters first in vivo and repeated these in the same heart and at identical sites in vitro. Methodological issues were tackled by using both unipolar and bipolar recordings. Physiological issues were explored by measuring both local and functional electrophysiological parameters. In 10 healthy dogs, 2 high-resolution needle electrodes were inserted into the left ventricle. Effective refractory periods (ERP) as well as activation recovery intervals (ARI) were determined at each electrode along both needles at basic cycle lengths (BCL) of 850 and 300 ms, respectively. After excision of the heart, ERP and ARI measurements were repeated in the arterially perfused wedge preparations. First, we observed that ERPs and ARIs were significantly shorter in vivo than in vitro. Mean ERPs and ARIs of all muscle layers were relatively uniform throughout the ventricular wall in vivo. The transition from the in vivo to the in vitro preparation was associated with a significant albeit small increase of mean ARIs in the subendocardium, whereas interlayer differences in mean ERPs did not reach statistical significance as in vivo.	Natural history of paediatric-onset ulcerative proctitis (UP) is poorly described. Our aim was to describe the phenotype and disease course of incident UP in a population-based study of paediatric-onset UC. All patients with UC diagnosed <17 years from 1988 to 2004, and followed during >2 years have been extracted from a population-based registry. UC location was defined according to the Paris classification. Cumulative risks for use of immunosuppressants (IS), anti-tumour necrosis factor alpha (TNF-α) therapy, colonic extension and colectomy were described using Kaplan-Meier method. Risk factors for colonic extension were assessed using Cox proportional hazards models. 158 patients with paediatric-onset UC (91 females) with a median age at diagnosis of 14.5 years (Q1: 11.4-Q3: 16.1) have been identified and followed during a median of 11.4 years (8.2-15.8). Among them, 25% had UP (E1) at diagnosis and 49% of them presented a colonic extension at maximal follow-up. In these children, the cumulative risk for colonic extension was 10% at 1 year, 45% at 5 years and 52% at 10 years. No parameter at diagnosis was associated with colonic extension in the UP (E1 group). IS use was significantly lower in patients with UP than in those with E2, E3 or E4 location (p=0.049). For the UP cohort, the cumulative risk for colectomy was 3% at 1 year, 10% at 5 years, 13% at 10 years and 13% at 15 years. Risks for colonic extension, treatment with anti-TNF-α and colectomy did not differ between the E1 group and the E2-E3-E4 group.
Does rapid intermittent compression increase skin circulation in chronically ischemic legs with infra-popliteal arterial obstruction?	Intermittent pneumatic compression (IPC) has been shown, by duplex, to increase popliteal artery flow in normal legs and in legs with superficial femoral artery occlusion. The objective of this study was to see if IPC improves distal circulation in legs with severe infra-popliteal disease. Sixteen chronically ischemic legs with arteriographically demonstrated crural or pedal disease were studied during compression with an ArtAssist compression-device. This device delivers rapid compression of the foot and calf. Cutaneous laser-Doppler flux was measured continuously at the dorsal aspect of the distal forefoot. The findings were compared to those in thirteen normal controls of similar age. In ischemic legs, the spontaneous changes in skin-flux are minimal: mean resting flux in sitting position was 0.87 +/- 0.46 AU (Arbitrary Units). Upon activation of the compression device the maximum flux increased to 4.55 +/- 1.35 AU. The difference was statistically significant (p < 0.001). This response was similar to that in normal controls.	Excess expression of acetylcholinesterase (AChE) in the cortex and hippocampus causes a decrease in the number of glutamatergic synapses and alters the expression of neurexin and neuroligin, trans-synaptic proteins that control synaptic stability. The molecular sequence and three-dimensional structure of AChE are homologous to the corresponding aspects of the ectodomain of neuroligin. This study investigated whether excess AChE interacts physically with neurexin to destabilize glutamatergic synapses. The results showed that AChE clusters colocalized with neurexin assemblies in the neurites of hippocampal neurons and that AChE co-immunoprecipitated with neurexin from the lysate of these neurons. Moreover, when expressed in human embryonic kidney 293 cells, N-glycosylated AChE co-immunoprecipitated with non-O-glycosylated neurexin-1β, with N-glycosylation of the AChE being required for this co-precipitation to occur. Increasing extracellular AChE decreased the association of neurexin with neuroligin and inhibited neuroligin-induced synaptogenesis. The number and activity of excitatory synapses in cultured hippocampal neurons were reduced by extracellular catalytically inactive AChE.
Do [ Analysis of distribution characteristics and drug resistance of 2748 strains of pathogens isolated from burn patients ]?	To provide epidemiological data of the distribution characteristics and drug resistance of the pathogens isolated from burn patients in recent years for guiding rational use of antibiotics in clinic. Totally 2748 strains of pathogens were isolated from 1977 specimens (blood, catheter, wound excretion, etc.) collected from 478 patients hospitalized in Institute of Burn Research of Southwest Hospital from March 2003 to June 2011. After being identified by API strips, drug resistance of the 2748 isolated pathogens to 55 commonly-used antibiotics including gentamicin, tobramycin, piperacillin, amikacin, etc. was tested by K-B paper disk diffusion method. The WHONET 5.3 software was used to analyze the following subjects: the distribution of the pathogens with different types and different sources each year, the changes in drug-resistant rates of Gram negative bacilli, Gram positive cocci, and fungi to several antibiotics, and the changes in sensitive rates of Pseudomonas aeruginosa (PA), Staphylococcus aureus (SA), Acinetobacter baumannii (AB), Candida albicans (CA) to several antibiotics. Among 2748 strains of pathogens, 1879 strains of Gram negative bacilli accounted for 68.38%, 628 strains of Gram positive cocci accounted for 22.85%, and 241 strains of fungi accounted for 8.77%. The isolation rate of strains from wound excretion ranked the first (1022 strains accounted for 37.19%), followed by those from respiratory tract (995 strains accounted for 36.21%) and blood (421 strains accounted for 15.32%). Strains isolated from other types of specimens were rare. Isolation rate of PA ranked the first (996 strains accounted for 36.24%), followed by SA (495 strains accounted for 18.01%) and AB (395 strains accounted for 14.37%). Isolation rate of AB showed a trend of increase year by year, but that of SA presented the opposite trend. Isolation rate of PA was quite stable. There were 484 strains of methicillin resistant SA among Staphylococci, accounting for 17.61%. Resistant rates of PA and AB to polymyxin B and polymyxin E were below 30.00%, and those of PA and AB to other antibiotics, such as the third generation cephalosporins, β-lactams, aminoglycosides, and quinolones, were from 57.91% to 100.00%. Resistant rate of AB to minocycline was 39.68%. From 2004 to 2011, sensitive rate of PA to quinolone antibiotics showed an increasing trend year by year, but that of AB to minocycline, netilmicin, imipenem, meropenem, tobramycin, and cefoperazone/sulbactam presented the opposite trend. Resistant rates of Enterococcus faecalis, Enterococcus faecium, and SA to teicoplanin and linezolid were less than 10.00%. Resistant rate of SA, Staphylococcus epidermidis and Enterococcus faecium to vancomycin was 0. Resistant rates of SA to quinupristin/dalfopristin, minocycline, fusidic acid, and compound sulfamethoxazole were low, respectively 0.82%, 9.35%, 2.21%, and 31.85%. Sensitive rates of SA to erythromycin, clindamycin, compound sulfamethoxazole, tetracycline, and minocycline showed an increasing trend year by year. Both infection rate and resistant rate of fungi were low. The resistant rates of CA to 5 kinds of antibiotics were less than 15.00%. The sensitive rate of CA to 5-flucytosine declined slightly, and those of CA to the other 4 antibiotics showed an increasing trend year by year.	While the intrauterine environment is essential for the health of offspring, the impact of high maternal serum estradiol (E2) on lipid metabolism in offspring and the mechanisms are unknown. We found that ovarian stimulation (OS) could result in high E2 levels in women throughout pregnancy. Strikingly, their newborns showed elevated total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels that were positively related with E2 in newborns. In vitro, E2 dose-dependently stimulated TC and LDL-C secretion, and increased expression of the cholesterol synthesis rate-limiting enzyme 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) in HepG2 cells and mouse fetal hepatocytes. In vivo, high maternal E2 was detected and fetal livers also showed significantly higher HMGCR expression in an OS mouse model. Notably, an estrogen response element (ERE) was identified in the HMGCR promoter, indicating that high maternal serum E2 could up-regulate HMGCR expression in fetal hepatocytes via an ERE that in turn induces elevated levels of TC and LDL-C in offspring.
Is anal cushion lifting method a novel radical management strategy for hemorrhoids that does not involve excision or cause postoperative anal complications?	To describe the anal cushion lifting (ACL) method with preliminary clinical results. Between January to September 2007, 127 patients who received ACL method for hemorrhoid was investigated with informed consent. In this study, three surgeons who specialized in anorectal surgery performed the procedures. Patients with grade two or more severe hemorrhoids according to Goligher's classification were considered to be indicated for surgery. The patients were given the choice to undergo either the ACL method or the ligation and excision method. ACL method is an original technique for managing hemorrhoids without excision. After dissecting the anal cushion from the internal sphincter muscle, the anal cushion was lifted to oral side and ligated at the proper position. Clinical characteristics and outcomes of patients were recorded including complications after surgery. A total of 127 patients were enrolled. Their median age was 42 (19-84) years, and 74.8% were female. In addition, more than 99% of the patients had grade 3 or worse hemorrhoids. The median follow-up period was 26 (0-88) mo, and the median operative time was 15 (4-30) min. After surgery, analgesics were used for a median period of three days (0-21). Pain control was achieved using extra-oral analgesic drugs, although some patients required intravenous injections of analgesic drugs. The median duration of the patients' postoperative hospital stay was 7 (2-13) d. A total of 10 complications (7.9%) occurred. Bleeding was observed in one patient and was successfully controlled with manual compression. Urinary retention occurred in 6 patients, but it disappeared spontaneously in all cases. Recurrent hemorrhoids developed in 3 patients after 36, 47, and 61 mo, respectively. No anal stenosis or persistent anal pain occurred.	Anaplastic thyroid carcinoma (ATC) is one of the most deadly human malignancies. It is 99% lethal, and patients have a median survival of only 6 months after diagnosis. Despite these grim statistics, the mechanism underlying the tumorigenic capability of ATC cells is unclear. S100A8 and S100A9 proteins have emerged as critical mediators in cancer. The aim was to investigate the expression and function of S100A8 and S100A9 in ATC and the mechanisms involved. We determined the expression of S100A8 and S100A9 in human ATC by gene array analysis and immunohistochemistry. Using RNAi-mediated stable gene knockdown in human ATC cell lines and bioluminescent imaging of orthotopic and lung metastasis mouse models of human ATC, we investigated the effects of S100A8 and S100A9 on tumorigenesis and metastasis. We demonstrated that S100A8 and S100A9 were overexpressed in ATC but not in other types of thyroid carcinomas. In vivo analysis in mice using ATC cells that had S100A8 knocked down revealed reduced tumor growth and lung metastasis, as well as significantly prolonged animal survival. Mechanistic investigations showed that S100A8 promotes ATC cell proliferation through an interaction with RAGE, which activates the p38, ERK1/2 and JNK signaling pathways in the tumor cells.
Does neuromuscular electrical stimulation-assisted gait increase muscle strength and volume in children with unilateral spastic cerebral palsy?	To determine if neuromuscular electrical stimulation (NMES) applied to the ankle dorsiflexors during gait improves muscle volume and strength in children with unilateral spastic cerebral palsy (CP). Thirty-two children (15 females, 17 males; mean age 10y 8mo, age range 5y 5mo-18y 1mo) with unilateral spastic CP and a Gross Motor Function Classification System of level I or level II were randomly assigned to either the 8-week daily NMES treatment group or control group (usual or conventional treatments). Outcomes at week 8 (post-NMES) and week 14 (carryover) included magnetic resonance imaging for muscle volumes (tibialis anterior, anterior compartment, and gastrocnemius), strength (hand-held dynamometry for isometric dorsiflexion strength and heel raises for functional strength), and clinical measures for lower limb selective motor control. At week 8, the treatment group demonstrated significantly (p<0.05) increased muscle volumes for tibialis anterior, anterior compartment, medial and lateral gastrocnemius, and dorsiflexion strength not only when compared to their baseline values but also when compared to the control group at week 8. At week 14, both tibialis anterior and lateral gastrocnemius volumes in the treatment group remained significantly increased when compared to their baseline values. However, only lateral gastrocnemius volumes had significantly greater values when compared to the control group at week 14. There were no between group differences in the clinical measures for lower limb selective motor control at week 8 and 14.	The prognosis for the hepatocellular carcinoma (HCC) patient is affected by invasion and metastases. The attenuated expression of adherens junction protein epithelial-cadherin (E-cad) correlates with a more malignant potential in HCC. However, the potential of the claudin (CL) family of tight junctional proteins for HCC prognosis has remained unrecognized. We immunohistochemically examined the expression of CL-1 and E-cad in resected specimens from 55 HCC cases. The percentage of CL-1- or E-cad-positive cells was counted in HCC cells and the surrounding hepatocytes and scored as 0 (0%), 1 (1-33%), 2 (34-66%), and 3 (67-100%). The expression of CL-1 or E-cad was considered "preserved" if the score in HCC was equal to or more than that in the surrounding hepatocytes, and "attenuated" if not so. In nontumorous tissue, CL-1 and E-cad were observed at the lateral surface of hepatocytes and biliary epithelial cells. In well-differentiated HCCs, the expression of CL-1 and E-cad was preserved in 12 of 14 cases. In poorly differentiated HCCs, E-cad expression was preserved in 9 of 18 cases, while CL-1 expression was preserved in only 4 cases (P<0.01 versus well-differentiated HCCs). HCCs with portal invasion showed significantly attenuated CL-1 expression than those without portal invasion (P<0.05). The survival rate after hepatectomy for HCC with attenuated CL-1 expression was significantly lower than that for HCC with preserved CL-1 expression.
Is glutamine infusion during ischemia detrimental in a murine gut ischemia/reperfusion model?	Gut ischemia/reperfusion (I/R) frequently occurs in clinical settings as a result of disproportionate splanchnic hypoperfusion during shock. Glutamine (GLN) supplementation of total parenteral nutrition (TPN) before gut I/R improves survival after gut I/R compared with standard TPN. However, it is unknown whether GLN treatment after the occurrence of the insult is beneficial or not. The aims of this study were to examine effects of GLN infusion during gut ischemia on survival, myeloid cell (neutrophils + monocytes) activation, and vascular permeability in organs. Male Institute of Cancer Research (ICR) mice were randomized to control and GLN groups. After IV cannulation, mice underwent 90 (experiments 1 and 2) or 60 (experiment 3) minutes of gut I/R. Control mice received normal saline infusion at 1 mL/h for 60 minutes during ischemia, whereas the GLN group was given 3% GLN solution. In experiment 1, survival rates were monitored for 72 hours (n = 25). In experiment 2, peripheral blood was obtained at 2 or 4 hours after reperfusion (n = 17). Reactive oxygen intermediate (ROI) production by myeloid cells was determined by flow cytometry using dihydrorhodamine 123 with or without phorbol myristate acetate stimulation. Expression of CD11a and CD11b on myeloid cells was also measured. Myeloperoxidase (MPO) activity in the lung was evaluated. In experiment 3, vascular permeability in organs was measured using Evans blue at 2 or 4 hours. In experiment 1, survival time in the GLN group was significantly reduced compared with the control group (p = .02, log-rank test). The survival rates were 92% (12/13) and 42% (5/12) for the control and GLN groups at 12 hours (p = .01) and 38% (5/13) and 0% (0/12) at 48 hours (p = .02), respectively. In experiment 2, ROI production was significantly higher in the GLN group than in the control group after PMA stimulation both at 2 and 4 hours. CD11b expression was significantly higher in the GLN group than in the control group at 4 hours. There was no difference in pulmonary MPO activity at either time point. In experiment 3, GLN infusion significantly increased hepatic vascular permeability compared with saline infusion at 4 hours.	Equine Multiple Congenital Ocular Anomalies (MCOA) syndrome consists of a diverse set of abnormalities predominantly localized to the frontal part of the eye. The disease is in agreement with a codominant mode of inheritance in our horse material. Animals presumed to be heterozygous for the mutant allele have cysts originating from the temporal ciliary body, peripheral retina and/or iris. In contrast, animals predicted to be homozygous for the disease-causing allele possess a wide range of multiple abnormalities, including iridociliary and/or peripheral retinal cysts, iridocorneal angle abnormalities, cornea globosa, iris hypoplasia and congenital cataracts. MCOA is most common in the Rocky Mountain horse breed where it occurs at a high frequency among Silver colored horses. The Silver coat color is associated with mutations in PMEL17 that resides on ECA6q23. To map the MCOA locus we analyzed 11 genetic markers on ECA6q and herein describe a chromosome interval for the MCOA locus. We performed linkage analysis within 17 paternal half-sib families of the Rocky Mountain horse breed. More than half of the 131 offspring had the Cyst phenotype and about one third had MCOA. Segregation data were obtained by genotyping 10 microsatellite markers most of which are positioned on ECA6q22-23, as well as the missense mutation for the Silver phenotype in PMEL17. Significant linkage was found between the MCOA locus and eight of the genetic markers, where marker UPP5 (Theta = 0, z = 12.3), PMEL17ex11 (Theta = 0, z = 19.0) and UPP6 (Theta = 0, z = 17.5) showed complete linkage with the MCOA locus. DNA sequencing of PMEL17 in affected and healthy control individuals did not reveal any additional mutations than the two mutations associated with the Silver coat color.
Does low-cost workflow improvement reduce gastrointestinal block use 17 % by altering classic histotechnology testing?	Gastrointestinal (GI) biopsy specimens were previously limited to four per cassette to facilitate established internal technical work practices and histotechnology best practice guidelines. We evaluated the workflow of these biopsy specimens. We implemented three specific changes: (1) up to 10 GI biopsy specimens could be placed in each cassette, (2) histotechnologists would no longer orient GI biopsy specimens, and (3) embedding would be in a straight line rather than diagonal. We evaluated the effects of these changes on total block numbers, quality of slides, and perceptions of staff. The mean number of cassettes used was reduced 17% for GI biopsy cases, or an overall decrease of 3% of total blocks processed by our histopathology laboratory. Slide quality was unchanged. Staff reported increased job satisfaction.	We showed earlier that statin treatment ameliorates target-organ injury in a transgenic model of angiotensin (Ang) II-induced hypertension. We now test the hypothesis that rosuvastatin (1, 10, and 50 mg/kg/day) influences leukocyte adhesion and infiltration, prevents induction of inducible nitric oxide synthase (iNOS), and ameliorates target-organ damage in a dose-dependent fashion. We treated rats harboring the human renin and human angiotensinogen genes (dTGR) from week 4 to 8 (n = 20 per group). Untreated dTGR developed severe hypertension, cardiac hypertrophy, and renal damage, with a 100-fold increased albuminuria and focal cortical necrosis. Mortality of untreated dTGR at age 8 weeks was 59%. Rosuvastatin treatment decreased mortality dose-dependently. Blood pressure was not affected. Albuminuria was reduced dose-dependently. Interstitial adhesion molecule (ICAM)-1 expression was markedly reduced by rosuvastatin, as were neutrophil and monocyte infiltration. Immunohistochemistry showed an increased endothelial and medial iNOS expression in small vessels, infiltrating cells, afferent arterioles, and glomeruli of dTGR. Immunoreactivity was stronger in cortex than medulla. Rosuvastatin markedly reduced the iNOS expression in both cortex and medulla. Finally, matrix protein (type IV collagen, fibronectin) expression was also dose- dependently reduced by rosuvastatin.
Are elevated serum levels of S-adenosylhomocysteine , but not homocysteine , associated with cardiovascular disease in stage 5 chronic kidney disease patients?	The putative role of sulfur amino acids such as homocysteine (tHcy) as cardiovascular risk factors is controversial in chronic kidney disease (CKD). Although, S-adenosylhomocysteine (SAH) levels have been linked to CVD in non-renal populations, such relationship has not been evaluated in CKD. Serum concentrations of S-adenosylmethionine (SAM), SAH and total homocysteine (tHcy) were determined by HPLC in 124 CKD stage 5 patients (GFR range 1-11 m/min) and 47 control subjects, and related to renal function, presence of CVD, inflammation and protein-energy wasting (PEW). The levels of SAM and SAH were higher in CKD patients than in controls. Both SAM (rho=-0.19; P<0.05) and SAH (rho=-0.37, P<0.001) were inversely related to GFR. The concentrations of SAH were significantly higher (P<0.001) in patients with CVD than in non-CVD patients, (683 (201-3057) vs 485 (259-2620) nmol/L; median (range)) as opposed to tHcy levels, which were lower in CVD patients. While SAH was not associated with the presence of inflammation or PEW, it was a significant contributor (OR; 4.9 (CI 1.8-12.8), P<0.001) to CVD in a multinomial logistic regression model (pseudo r(2)=0.31).	This study aimed to evaluate the long-term outcomes and the soft-tissue response to osseous genioplasty in patients with chin retrusion caused by early life facial burn injury. Twenty-two consecutive patients with retrusive chin as a result of severe childhood facial burn were included in this study. Cephalometric analysis and photographs were used to assess the patients for eligibility of a surgical correction. Horizontal hard-tissue advancement and soft-tissue responses were measured as the primary outcomes at the early and late postoperative follow-up visits. A total of 22 patients fulfilled the study requirements. Average preoperative distance between the pogonion, as the most anterior point of the anterior mandibular contour, and a perpendicular line connecting the nasion and the supramental point of the mandible was 0.82 ± 1.1 mm, which increased significantly to 7.8 ± 0.8 mm after genioplasty (p < 0.0001). Soft tissue was repositioned on average 6.1 ± 0.4 mm anteriorly on average, which is in comparison with the amount of chin skeleton advancement, and a response ratio of 0.8:1 was calculated at late follow-up.
Does intracoronary shunt prevent ischemia in off-pump coronary artery bypass surgery?	The purpose of this study was to evaluate the role of intracoronary shunt during off-pump coronary artery bypass surgery. Fifty-six patients undergoing off-pump coronary artery bypass using the left internal mammary artery to bypass the left anterior descending coronary artery were randomly assigned to have the bypass performed with intracoronary shunt or by occlusive snaring. Ischemia during grafting was monitored by tissue Doppler. Hemodynamic status and indicators of ischemia were monitored, and on-table and postoperative angiography were performed. In patients with retrograde filling of the left anterior descending coronary artery, ischemia did not develop, but occlusion of antegradely perfused vessels caused ischemia in 26 of 33 patients. Ischemia was reversed in 14 of 16 shunted patients, and in 3 of 17 nonshunted cases (p = 0.004). Angiography showed a trend toward improved on-table angiographic results in shunted patients. After 3 months, graft patency was 100%, but 1 patient treated without shunt required reintervention and 15 patients had new angiographic lesions, equally distributed between shunted and nonshunted patients.	Endoplasmic reticulum (ER) stress is involved in liver injury, but molecular determinants are largely unknown. This study investigated the role of pleckstrin homology-like domain, family A, member-3 (PHLDA3), in hepatocyte death caused by ER stress and the regulatory basis. Hepatic PHLDA3 expression was assessed in HCV patients with hepatitis and in several animal models with ER stress. Immunoblottings, PCR, reporter gene, chromatin immunoprecipitation (ChIP) and mutation analyses were done to explore gene regulation. The functional effect of PHLDA3 on liver injury was validated using lentiviral delivery of shRNA. PHLDA3 was overexpressed in relation to hepatocyte injury in patients with acute liver failure or liver cirrhosis or in toxicant-treated mice. In HCV patients with liver injury, PHLDA3 was upregulated in parallel with the induction of ER stress marker. Treatment of mice with tunicamycin (Tm) (an ER stress inducer) increased PHLDA3 expression in the liver. X box-binding protein-1 (Xbp1) was newly identified as a transcription factor responsible for PHLDA3 expression. Inositol-requiring enzyme 1 (IRE1) (an upstream regulator of Xbp1) was required for PHLDA3 induction by Tm, whereas other pathways (c-Jun N-terminal kinase (JNK), protein kinase RNA-like endoplasmic reticulum kinase (PERK) and activating transcription factor 6 (ATF6)) were not. PHLDA3 overexpression correlated with the severity of hepatocyte injury in animal or cell model of ER stress. In p53-deficient cells, ER stress inducers transactivated PHLDA3 with a decrease in cell viability. ER stress-induced hepatocyte death depended on serine/threonine protein kinase B (Akt) inhibition by PHLDA3. Lentiviral delivery of PHLDA3 shRNA to mice abrogated p-Akt inhibition in the liver by Tm, attenuating hepatocyte injury.
Is a banana aquaporin gene , MaPIP1 ; 1 , involved in tolerance to drought and salt stresses?	Aquaporin (AQP) proteins function in transporting water and other small molecules through the biological membranes, which is crucial for plants to survive in drought or salt stress conditions. However, the precise role of AQPs in drought and salt stresses is not completely understood in plants. In this study, we have identified a PIP1 subfamily AQP (MaPIP1;1) gene from banana and characterized it by overexpression in transgenic Arabidopsis plants. Transient expression of MaPIP1;1-GFP fusion protein indicated its localization at plasma membrane. The expression of MaPIP1;1 was induced by NaCl and water deficient treatment. Overexpression of MaPIP1;1 in Arabidopsis resulted in an increased primary root elongation, root hair numbers and survival rates compared to WT under salt or drought conditions. Physiological indices demonstrated that the increased salt tolerance conferred by MaPIP1;1 is related to reduced membrane injury and high cytosolic K+/Na+ ratio. Additionally, the improved drought tolerance conferred by MaPIP1;1 is associated with decreased membrane injury and improved osmotic adjustment. Finally, reduced expression of ABA-responsive genes in MaPIP1;1-overexpressing plants reflects their improved physiological status.	The aim of this study was to investigate whether risk factors for embolism would promote thrombus formation in patients with nonvalvular atrial fibrillation (NVAF). Hemostatic markers for platelet activity (ie, platelet factor-4 and beta-thromboglobulin [TG]), thrombotic status (ie, prothombin fragments 1 and 2), and fibrinolytic status (ie, d-dimer) were determined in 246 patients with NVAF (mean age, 66.1 years) and 111 control subjects without NVAF (68.3 years). The beta-TG level was higher in NVAF patients than in control subjects. D-dimer levels were higher in NVAF patients having risk factors (mean [+/- SE] d-dimer level, 158.6 +/- 9.2 ng/mL) than in those without risk factors (mean d-dimer level, 92.1 +/- 6.7 ng/mL; p < 0.01) and in control subjects (mean d-dimer level: control subjects with risk factors, 79.1 +/- 10.3 ng/mL; control subjects without risk factors, 31.0 +/- 7.4 ng/mL; p < 0.01). NVAF (odds ratio [OR], 3.94; 95% confidence interval [CI], 1.87 to 8.30; p = 0.0003) and age of >/= 75 years (OR, 5.68; 95% CI, 2.87 to 11.23; p < 0.0001) emerged as predictors of elevated levels of d-dimer, and only NVAF (OR, 10.30; 95% CI, 5.67 to 18.72; p < 0.0001) emerged as a predictor of elevated levels of beta-TG.
Do the Influence of an undergraduate scientific initiation programme onn the professional profile of new physicians?	This paper studies the influence of a Scientific Initiation Programme (SIP) on the professional profile of new doctors from a Brazilian university. Evaluate fifty-two new doctors divided into two groups matched by sex, age and academic performance and differing only in participation in the SIP. Professional and socioeconomic data were collected, including schooling of parents; average income before, during and after the medical course; current professional situation; results of exams for civil servant recruitment; and titles and degrees obtained after graduation. Significant differences were found only in civil servant recruitment exam results (p=0.0098) and in income after graduation (p=0.02), which were both higher in the non-SIP group. Only one doctor got a M.Sc. degree after graduation, but many of them in both groups obtained technical titles, and had papers presented at congresses or published.	Acute lung injury (ALI) induced by excessive hyperoxia has been employed as a model of oxidative stress imitating acute respiratory distress syndrome. Under hyperoxic conditions, overloading quantities of reactive oxygen species (ROS) are generated in both lung epithelial and endothelial cells, leading to ALI. Some NADPH oxidase (NOX) family enzymes are responsible for hyperoxia-induced ROS generation in lung epithelial and endothelial cells. However, the molecular mechanisms of ROS production in type II alveolar epithelial cells (AECs) and ALI induced by hyperoxia are poorly understood. In this study, we show that dual oxidase 2 (DUOX2) is a key NOX enzyme that affects hyperoxia-induced ROS production, particularly in type II AECs, leading to lung injury. In DUOX2 mutant mice (DUOX2(thyd/thyd)) or mice in which DUOX2 expression is knocked down in the lungs, hyperoxia-induced ALI was significantly lower than in wild-type (WT) mice. DUOX2 was mainly expressed in type II AECs, but not endothelial cells, and hyperoxia-induced ROS production was markedly reduced in primary type II AECs isolated from DUOX2(thyd/thyd) mice. Furthermore, DUOX2-generated ROS are responsible for caspase-mediated cell death, inducing ERK and JNK phophorylation in type II AECs. To date, no role for DUOX2 has been defined in hyperoxia-mediated ALI despite it being a NOX homologue and major ROS source in lung epithelium.
Does chronic lipoic acid treatment worsen energy imbalances in streptozotocin-induced diabetic rats?	Our objective was to verify the energy balance in streptozotocin-induced diabetic rats chronically treated with lipoic acid (LA). Diabetes was induced in rats by streptozotocin and the animals divided into four groups, comprising controls and diabetic rats, with each group receiving either daily intraperitoneal LA (30 mg/kg) or a buffer solution for 30 days. Body weight, food intake and stool and urine collections were recorded daily. On day 30, animals were sacrificed and the carcasses, faeces and urine collected and processed for calorimetric analysis. Blood glucose and insulin were also determined. All parameters of energy balance were affected by diabetes. LA treatment reduced weight gain, energy gain and gross food efficiency in both control and diabetic animals. However, the LA-treated animals tended to show higher energy expenditure than non-treated animals. Body composition was also affected by diabetes: fat content was impaired by LA treatment in both control and diabetic animals. The latter also showed increased glycaemia and decreased insulinaemia, but LA had no effect on these parameters.	To explore the effect of epidermal growth factor-like domain 7(EGFL7) on the migration and angiogenesis of endothelial cells. EGFL7 overexpression vectors were constructed and transfected into human microvascular endothelial cells. The expression levels of EGFL7-mRNA and EGFL7 protein were examined by real-time RT-PCR and Western blot. Cell migration was analyzed by the wound healing. The capability of cell to form capillary-like tubes in vitro was evaluated on matrigel assay. Protein expression of p-AKT, AKT, p-ERK and ERK in endothelial cells was detected by Western blot upon transfection with EGFL7 overexpression vectors and vehicle control for 0, 10, 30 and 60 min. Migration and angiogenesis of endothelial cells were notably enhanced by EGFL7 overexpression. ERK pathway was strongly activated by EGFL7, whereas AKT remained constant in endothelial cells. Inhibition of ERK impaired EGFL7 induced ERK activation and endothelial cell migration and angiogenesis.
Does impact on survivors of retinoblastoma when informed of study result on risk of second cancers?	To assess the impact of providing research feedback to retinoblastoma survivors or their parents regarding the risk of second cancers. A four-page survey was sent to 801 retinoblastoma survivors and 55 parents to ascertain their reactions to a "results-letter." The "results-letter" provided feedback from a study indicating that retinoblastoma survivors may be at increased risk of second cancers. Three hundred and thirty-nine (339) retinoblastoma survivors and 43 parents responded to the survey. Eighty-four percent (84%) of respondents found the "results-letter" "very" to "extremely" understandable and 72% found it "very" to "extremely" useful. Participants scored "very" to "extremely" to the following emotions: frightened = 28%, anxious = 27%, sad = 25%, overwhelmed = 15%, angry = 11%, and guilty = 6%. Five (1.4%) respondents stated that they would have preferred not to receive the results. Responses did not vary significantly between survivors with different risks of second cancers. No significant differences were observed between males and females. However, parents were significantly more likely to report feelings of anxiety, guilt, anger, being overwhelmed, and frightened compared to adult retinoblastoma survivors (P < 0.05). Individuals with less than a college education were significantly more sad, angry, overwhelmed, and frightened by the information than individuals with a college degree or higher (P < 0.05). Eighteen percent (18%) of all respondents shared the feedback with their physician. The method of choice for receiving results was by letter with contact names and phone numbers.	Several pathogenic bacteria utilize receptors of the CEACAM family to attach to human cells. Binding to different members of this receptor family can result in uptake of the bacteria. Uptake of Neisseria gonorrhoeae, a gram-negative human pathogen, via CEACAMs found on epithelial cells, such as CEACAM1, CEA or CEACAM6, differs mechanistically from phagocytosis mediated by CEACAM3, a CEACAM family member expressed selectively by human granulocytes. We find that CEACAM1- as well as CEACAM3-mediated bacterial internalization are accompanied by a rapid increase in phosphatidylinositol-3,4,5 phosphate (PI(3,4,5)P) at the site of bacterial entry. However, pharmacological inhibition of phosphatidylinositol-3' kinase (PI3K) selectively affects CEACAM1-mediated uptake of Neisseria gonorrhoeae. Accordingly, overexpression of the PI(3,4,5)P phosphatase SHIP diminishes and expression of a constitutive active PI3K increases CEACAM1-mediated internalization of gonococci, without influencing uptake by CEACAM3. Furthermore, bacterial uptake by GPI-linked members of the CEACAM family (CEA and CEACAM6) and CEACAM1-mediated internalization of N. meningitidis by endothelial cells require PI3K activity. Sensitivity of CEACAM1-mediated uptake toward PI3K inhibition is independent of receptor localization in cholesterol-rich membrane microdomains and does not require the cytoplasmic or the transmembrane domain of CEACAM1. However, PI3K inhibitor sensitivity requires the Ig(C2)-like domains of CEACAM1, which are also present in CEA and CEACAM6, but which are absent from CEACAM3. Accordingly, overexpression of CEACAM1 Ig(C2) domains blocks CEACAM1-mediated internalization.
Is scalp hypothermia to prevent chemotherapy-induced alopecia effective and safe : a pilot study of a new digitized scalp-cooling system used in 74 patients?	The aim of this study was to examine the efficacy and safety of a new digitized, controlled, scalp-cooling system to prevent chemotherapy-induced alopecia. Seventy-four female cancer patients who received 13 varying chemotherapy regimens were included in a nonrandomized pilot study. The Digni 2-3 with Dignicap system consists of a refrigerator unit and a control unit integrated into a mobile cabinet and connected to a tight-fitting cooling cap. This system maintains a constant scalp temperature of +5 degrees C for many hours. In this study, 60 patients were treated for ovarian cancer with either taxane or epirubicin combination chemotherapy. Eight patients with Hodgkin's lymphoma, three with breast cancer, two with endometrial cancer, and one with sarcoma were also included. Photo documentation and patient assessment of hair loss and discomfort were performed. In anthracycline-treated patients, total prevention of hair loss was observed, whereas hair loss in paclitaxel/docetaxel-treated patients was minimal to none. The combination of anthracycline and taxane resulted in more hair loss, but only three of six patients used a wig. Scalp cooling was generally very well tolerated; only two of 74 patients discontinued use of the cold cap due to discomfort. No scalp metastases occurred over a median follow-up period of 15 months.	Elevated levels of B-type natriuretic peptide (BNP) are associated with adverse clinical outcomes in acute coronary syndrome (ACS), but several questions remain outstanding. Firstly, it has not yet been determined whether an additional BNP sample at 7 weeks post ACS would enhance risk prediction. Secondly, we assessed whether the prognostic potential of BNP in ACS could be explained by echocardiographic abnormalities such as left ventricular hypertrophy (LVH). We measured bedside BNP levels in 443 consecutive patients presenting with ACS and at 7 weeks outpatient follow-up. Main outcome measure was either all-cause mortality, readmission with ACS, or congestive heart failure) at 10 months from presentation. Of the 443 patients, 120 patients presented with ST-elevation myocardial infarction (27%). There were 90 cardiovascular (CV) events at 10 months. Adjusting for age, sex, hypertension, diabetes mellitus, smoking status, renal dysfunction, left ventricular ejection fraction, and echocardiographic LVH elevated near patient BNP levels (>80 pg/mL) were still associated with subsequent CV events when measured on admission (adjusted relative risk [RR] 2.63 [95% CI 1.34-5.19)] and also at 7 weeks post ACS (adjusted RR 4.12 [95% CI 1.58-10.72]). Patients with persistent BNP elevation at 7 weeks were also at an increased risk of CV events compared to those with an initial high BNP which then fell (unadjusted RR 4.04 [95% CI 1.24-13.15]).
Is ulcerative proctitis a frequent location of paediatric-onset UC and not a minor disease : a population-based study?	Natural history of paediatric-onset ulcerative proctitis (UP) is poorly described. Our aim was to describe the phenotype and disease course of incident UP in a population-based study of paediatric-onset UC. All patients with UC diagnosed <17 years from 1988 to 2004, and followed during >2 years have been extracted from a population-based registry. UC location was defined according to the Paris classification. Cumulative risks for use of immunosuppressants (IS), anti-tumour necrosis factor alpha (TNF-α) therapy, colonic extension and colectomy were described using Kaplan-Meier method. Risk factors for colonic extension were assessed using Cox proportional hazards models. 158 patients with paediatric-onset UC (91 females) with a median age at diagnosis of 14.5 years (Q1: 11.4-Q3: 16.1) have been identified and followed during a median of 11.4 years (8.2-15.8). Among them, 25% had UP (E1) at diagnosis and 49% of them presented a colonic extension at maximal follow-up. In these children, the cumulative risk for colonic extension was 10% at 1 year, 45% at 5 years and 52% at 10 years. No parameter at diagnosis was associated with colonic extension in the UP (E1 group). IS use was significantly lower in patients with UP than in those with E2, E3 or E4 location (p=0.049). For the UP cohort, the cumulative risk for colectomy was 3% at 1 year, 10% at 5 years, 13% at 10 years and 13% at 15 years. Risks for colonic extension, treatment with anti-TNF-α and colectomy did not differ between the E1 group and the E2-E3-E4 group.	Rapid ventricular pacing produces a reliable model of heart failure. Cessation after 4 weeks of rapid ventricular pacing results in rapid normalization of left ventricular function, but the left ventricle remains persistently dilated. We present novel data that show that prolonged rapid ventricular pacing (10 weeks) creates a model of chronic left ventricular dysfunction. In 9 dogs undergoing 10 weeks of rapid ventricular pacing, left ventricular function and volumes were serially assessed by using 2-dimensional echocardiography and pressure-volume analysis for 12 weeks after cessation of pacing. Increased end-diastolic volume and decreased systolic and diastolic function were seen at the end of pacing. By 2 weeks of recovery from rapid ventricular pacing, end-diastolic volume and ejection fraction were partially recovered but did not improve further thereafter. Load-independent and load-sensitive indices of function obtained by pressure-volume analysis at 8 and 12 weeks of recovery confirmed a persistence of both systolic and diastolic dysfunction. In addition, left ventricular mass increased with pacing and remained elevated at 8 and 12 weeks of recovery. Four of these dogs studied at 6 months of recovery showed similar left ventricular abnormalities.
Is harm avoidance associated with progression of parkinsonism in community-dwelling older adults : a prospective cohort study?	We tested the hypothesis that harm avoidance, a trait associated with behavioral inhibition, is associated with the rate of change in parkinsonism in older adults. At baseline harm avoidance was assessed with a standard self-report instrument in 969 older people without dementia participating in the Rush Memory and Aging Project, a longitudinal community-based cohort study. Parkinsonism was assessed annually with a modified version of the motor section of the Unified Parkinson's Disease Rating Scale (mUPDRS). Average follow-up was 5 years. A linear mixed-effects model controlling for age, sex and education showed that for an average participant (female, 80 years old at baseline, with 14 years of education and a harm avoidance score of 10), the overall severity of parkinsonism increased by about 0.05 unit/ year (Estimate, 0.054, S.E., 0.007, p <0.001) and that the level of harm avoidance was associated with the progression of parkinsonism (Estimate, 0.004, S.E., 0.001, p <0.001). Thus, for an average participant, every 6 point (~1 SD) increase in harm avoidance score at baseline, the rate of progression of parkinsonism increased about 50% compared to an individual with an average harm avoidance score. This amount of change in parkinsonism over the course of the study was associated with about a 5% increased risk of death. The association between harm avoidance and progression of parkinsonism persisted when controlling for cognitive function, depressive symptoms, loneliness, neuroticism, late-life cognitive, social and physical activities and chronic health conditions.	Bacillus Calmette-Guerin (BCG) binds to the tumor cell as a result of mycobacterial receptors for fibronectin (FN). Cell surface bound FN serves as a bridge through which BCG attaches to the tumor cell. Despite the importance of FN studies have demonstrated an idiosyncratic decrease in BCG adherence in response to exogenous FN. We evaluated the effect of exogenous and autocrine FN on the ability of BCG to adhere to the tumor cell surface and initiate cellular signaling. BCG adherence to parental 253J and FN over expressing 253JTGFbeta1-8 cells as well as to the intrinsic FN expressing cell line 647V was quantified using green fluorescent protein-BCG. Experiments were performed to assess the effect of FN on BCG initiated signal transduction through nuclear factor kappaB and AP1. Finally, the integrity of the BCG activated signaling pathway in transforming growth factor-beta1/FN over expressors was assessed using antibody mediated cross-linking of the FN receptor. BCG adherence was decreased in cell lines with high autocrine expression of FN. Exogenous FN prevented BCG induced transactivation of nuclear factor kappaB and AP1 reporter constructs. No BCG stimulated signaling to these reporters could be detected in FN over expressing 253J cells. NonFN dependent alpha5beta1 cross-linking initiated signal transduction in FN over expressing cells.
Does the association of telomere length with colorectal cancer differ by the age of cancer onset?	Telomeres are nucleoprotein structures that cap the end of chromosomes and shorten with sequential cell divisions in normal aging. Short telomeres are also implicated in the incidence of many cancers, but the evidence is not conclusive for colorectal cancer (CRC). Therefore, the aim of this study was to assess the association of CRC and telomere length. In this case-control study, we measured relative telomere length from peripheral blood leukocytes (PBLs) DNA with quantitative PCR in 598 CRC patients and 2,212 healthy controls. Multivariate analysis indicated that telomere length was associated with risk for CRC, and this association varied in an age-related manner; younger individuals (≤50 years of age) with longer telomeres (80-99 percentiles) had a 2-6 times higher risk of CRC, while older individuals (>50 years of age) with shortened telomeres (1-10 percentiles) had 2-12 times the risk for CRC. The risk for CRC varies with extremes in telomere length in an age-associated manner.	Endothelin-1 (ET-1) is the most powerful factor known to release atrial natriuretic peptide (ANP) in vivo and in cultured cardiac myocytes or preparations of atrium. We tested the role of endogenous ET-1 in the regulation of ANP release by passive immunization in anesthetized rats. Intravenous injection of antiserum against ET-1 was shown to decrease basal and volume-stimulated plasma concentrations of ANP, whereas control serum was without effect. Antiserum generated in rabbits cross-reacted 100% with endothelin-2 and -3. In pentobarbital-anesthetized Wistar rats treated with ET-1 antiserum, plasma ANP concentration measured by radioimmunoassay was reduced by 37% from starting level after 10 minutes and by 30% after 60 minutes. Control rat serum had no effect on plasma ANP. Rapid intravenous infusion of 8 mL of 0.9% NaCl caused a sixfold increase of plasma ANP concentration in control rats but only twofold in rats pretreated with ET-1 antiserum (P < .01). This effect of ET-1 antiserum was dose dependent. ET-1 antiserum changed neither blood pressure nor heart rate significantly in anesthetized rats. Pretreatment with ET-1 antiserum did not affect the initial hypotensive response to intravenous ET-1 0.5 nmol/kg but significantly attenuated the subsequent hypertensive response to endothelin.
Are diets lower in folic acid and carotenoids associated with the coronary disease epidemic in Central and Eastern Europe?	To test our hypothesis that lower intakes of previously identified cardioprotective nutrients would be associated with the coronary epidemic in Central and Eastern Europe. We conducted a survey of coronary mortality in 16 countries and diet in 19 countries. Countries were placed in four groups with different cultural patterns (Central and Eastern Europe, including Russia; Western Europe and the United States; Mediterranean; and Asian). Independent predictors of coronary mortality. Means and standard deviations were calculated, and analysis of variance with Bonferroni post hoc tests and backward elimination regression analysis was conducted. Coronary mortality was highest in Central and Eastern Europe followed by Western Europe and the United States, the Mediterranean countries, and Asia (Japan). The model with folate, fiber, and n-6/n-3 fatty acids explained the majority of variation in coronary mortality (men 86%, women 90%). Most of the variation was explained by folate (men 61%, women 62%). The picture is complicated by the fact that folate, lutein/zeaxanthin, and beta-carotene were highly intercorrelated ( r =0.87 to 0.99).	Hemostatic agents, tissue adhesives and sealants may contribute to a reduction in hemorrhage-associated morbidity and mortality. Towards this end, we have recently developed a lysine-based dendritic hydrogel (PEG-LysNH2) that can potentially be used in the management of severe trauma and/or intraoperative bleeding. As a first step in demonstrating the potential utility of this approach, our objective was to ascertain the ability of the PEG-LysNH2 to adhere to and seal injured tissues, as well as to maintain the seal under physiological conditions. The efficacy of the PEG-LysNH2 in sealing injured tissues was evaluated using an ex-vivo pressure testing system. A 2.5 mm incision was made on intact ex-vivo tissues and then sealed with the PEG-LysNH2. Application of the PEG-LysNH2 was followed by 1) step-wise pressure increase to a maximum of 250 mmHg and 2) fluctuating pressures, between 100-180 mmHg with a rate of 3 Hz, over a 24-hour period. The performance of the PEG-LysNH2 was compared to those of commercially available sealants and adhesives. During gradual pressure increase, mean pressures at 30 seconds (P30) ranged between 206.36 - 220.17 mmHg for the sealants, and they were greater than control and suture groups (p < 0.01 and p = 0.013, respectively). Additionally, all products held under fluctuating pressures: mean pressures ranged between 135.20 - 160.09 mmHg, and there were no differences observed between groups (p = 0.96).
Are fundus autofluorescence lifetimes increased in non-proliferative diabetic retinopathy?	To discriminate non-proliferative diabetic retinopathy (NPDR) patients from healthy controls by fluorescence lifetime imaging ophthalmoscopy (FLIO). A prototype FLIO (Heidelberg-Engineering, Heidelberg, Germany) was used to examine the retina of 33 patients and 28 controls. As increased fluorescence of the diabetic lens is known, the lenses of 34 patients and 24 controls were investigated as well. Time-resolved decay was detected in two spectral channels (ch1: 498-560 nm, ch2: 560-720 nm) and approximated by a series of three exponential functions yielding in lifetimes (τ Significant differences between patients and controls were found for all fundus lifetime components (τ	Multiple rib fractures cause significant pain and potential for chest wall instability. Despite an emerging trend of surgical management of flail chest injuries, there are no studies examining the effect of rib fracture fixation on respiratory function. Using a novel full thorax human cadaveric breathing model, we sought to explore the effect of flail chest injury and subsequent rib fracture fixation on respiratory outcomes. We used five fresh human cadavers to generate negative breathing models in the left thorax to mimic physiologic respiration. Inspiratory volumes and peak flows were measured using a flow meter for all three chest wall states: intact chest, left-sided flail chest (segmental fractures of ribs 3 - 7), and post-fracture open reduction and internal fixation (ORIF) of the chest wall with a pre-contoured rib specific plate fixation system. A wide variation in the mean inspiratory volumes and peak flows were measured between specimens; however, the effect of a flail chest wall and the subsequent internal fixation of the unstable rib fractures was consistent across all samples. Compared to the intact chest wall, the inspiratory volume decreased by 40 ± 19% in the flail chest model (P = 0.04). Open reduction and internal fixation of the flail chest returned the inspiratory volume to 130 ± 71% of the intact chest volumes (P = 0.68). A similar 35 ± 19% decrease in peak flows was seen in the flail chest (P = 0.007) and this returned to 125 ± 71% of the intact chest following ORIF (P = 0.62).
Does miR-494 act as an anti-oncogene in gastric carcinoma by targeting c-myc?	We recently showed that miR-494 was downregulated in gastric carcinoma (GC). The objectives of this study were to determine the role of miR-494 in GC malignancy and to identify its target genes. Real-time polymerase chain reaction was employed to quantify the expression level of miR-494 and c-myc in gastric cancer tissues. Bioinformatics was used to predict the downstream target genes of miR-494, which were confirmed by luciferase and RNA immunoprecipitation assays. Cell functional analyses and a xenograft mouse model were used to evaluate the role of miR-494 in malignancy. miR-494 was downregulated in human GC tissues and in GC cells and was negatively correlated with c-myc expression. High level of c-myc or low level of miR-494 correlated with poor prognosis. The miR-494-binding site in the c-myc 3' untranslated region was predicted using TargetScan and was confirmed by the luciferase assay. Additionally, c-myc and miR-494 were enriched in coimmunoprecipitates with tagged Argonaute2 proteins in cells overexpressing miR-494. Furthermore, a miR-494 mimic significantly downregulated endogenous c-myc expression, which may contribute to the delayed G1/S transition, decreased synthesis phase bromodeoxyuridine incorporation, and impaired cell growth and colony formation; on the other hand, treatment with a miR-494 inhibitor displayed the opposite effects. Reduced tumor burden and decreased cell proliferation were observed following the delivery of miR-494 into xenograft mice.	Recent guidelines suggest supplementation with ergocalciferol (vitamin D(2)) in chronic kidney disease stages 3 and 4 patients with elevated parathyroid hormone (PTH) levels and 25-hydroxyvitamin D (25OHD) levels <75 nmol/l. These guidelines are also applied to renal transplant patients. However, the prevalence rates of 25OHD deficiency and its association with PTH levels in renal transplant populations have not been extensively examined. We aimed to document the prevalence rates of 25OHD deficiency [defined by serum levels <40 nmol/l (<16 ng/ml)] and insufficiency [<75 nmol/l (<30 ng/ml)] in a single renal transplant centre, and examine its relationship with PTH levels. Serum 25OHD and PTH concentrations were measured in 419 transplant patients attending a single renal transplant clinic over a 4-month period. Demographic and biochemical data were also collected, including serum creatinine, calcium, phosphate and albumin. Simple and multiple linear regression analysis were performed. In 27.3% of the patients, 25OHD deficiency was present, and 75.5% had insufficiency. On univariate analysis, 25OHD, serum albumin and estimated glomerular filtration rate (eGFR) were significantly associated with PTH levels (P < 0.0001, P = 0.004 and P < 0.0001, respectively). Multiple linear regression demonstrated that only 25OHD, eGFR and serum phosphate were significantly predictive of PTH levels (R(2) = 0.19, P < 0.0001). In this model, a 75 nmol/l increase in 25OHD will only result in a maximal reduction in PTH of 2.0 pmol/l.
Does the renin-angiotensin system promote arrhythmogenic substrates and lethal arrhythmias in mice with non-ischaemic cardiomyopathy?	The progression of pathological left ventricular remodelling leads to cardiac dysfunction and contributes to the occurrence of malignant arrhythmias and sudden cardiac death. The underlying molecular mechanisms remain unclear, however. Our aim was to examine the role of the renin-angiotensin system (RAS) in the mechanism underlying arrhythmogenic cardiac remodelling using a transgenic mouse expressing a cardiac-specific dominant-negative form of neuron-restrictive silencer factor (dnNRSF-Tg). This mouse model exhibits progressive cardiac dysfunction leading to lethal arrhythmias. Subcutaneous administration of aliskiren, a direct renin inhibitor, significantly suppressed the progression of pathological cardiac remodelling and improved survival among dnNRSF-Tg mice while reducing arrhythmogenicity. Genetic deletion of the angiotensin type 1a receptor (AT1aR) similarly suppressed cardiac remodelling and sudden death. In optical mapping analyses, spontaneous ventricular tachycardia (VT) and fibrillation (VF) initiated by breakthrough-type excitations originating from focal activation sites and maintained by functional re-entry were observed in dnNRSF-Tg hearts. Under constant pacing, dnNRSF-Tg hearts exhibited markedly slowed conduction velocity, which likely contributes to the arrhythmogenic substrate. Aliskiren treatment increased conduction velocity and reduced the incidence of sustained VT. These effects were associated with suppression of cardiac fibrosis and restoration of connexin 43 expression in dnNRSF-Tg ventricles.	To investigate the contribution of muscle mass and handgrip strength in predicting the functional outcome after hip fracture in women. Observational study. Rehabilitation hospital. White women (N=123 of 149) who were consecutively admitted to a rehabilitation hospital because of their first fracture of the hip. Not applicable. We measured appendicular lean mass (aLM) by dual-energy x-ray absorptiometry (DXA) 21.1 ± 8.7 (mean ± SD) days after hip fracture occurrence in the 123 women. On the same day, we assessed grip strength at the nondominant arm with a dynamometer. At the end of acute inpatient rehabilitation we measured the ability to function in activities of daily living by using the Barthel Index, and lower limb performance by using the Timed Up and Go (TUG) test. We found significant correlations between handgrip strength measured before rehabilitation and Barthel Index scores after rehabilitation (ρ=.50; P<.001), Barthel Index effectiveness (ρ=.45; P<.001), and the TUG test (ρ=-.41; P<.001). Conversely, we found no significant correlations between aLM/height(2) and Barthel Index scores after rehabilitation (ρ=.075; P=.41), Barthel Index effectiveness (ρ=.06; P=.53), or the TUG test (ρ=.005; P=.96). Significant associations between grip strength and all the outcome measures persisted after adjustment for 8 potential confounders, including Barthel Index scores before rehabilitation, age, number of medications, number of comorbidities, pressure ulcers, concomitant infections, time between fracture occurrence and assessment, and aLM/height(2).
Is topical clobetasol in conjunction with topical tretinoin effective in preventing scar formation after superficial partial-thickness burn ulcers of the skin : A retrospective study?	Deep erythema and inflammation after re-epithelialization of superficial wounds is a sign of scar formation. Corticosteroids may prevent scarring by suppression of inflammation and fibroblast activity. Tretinoin may increase the efficacy of corticosteroids in this setting. To evaluate the efficacy of corticosteroids plus tretinoin for prevention of scars after superficial wounds. In a retrospective study of patients with superficial partial thickness thermal skin burn, we compared the patients who received clobetasol plus tretinoin after re-epithelialization with patients who did not receive any medication. Clobetasol propionate 0.05% ointment was used twice daily with overnight occlusive dressing in conjunction with twice weekly topical tretinoin 0.05% cream. Among 43 patients who had light pink or no erythema after re-epithelialization and consequently did not receive clobetasol + tretinoin, no scar was developed. Among patients who had deep erythema after re-epithelialization, rate of scar formation was significantly higher in 14 patients who did not receive clobetasol + tretinoin than in 21 patients who received clobetasol + tretinoin (64% and 19%, respectively; p = 0.01).	There is a debate about the influence of executive functioning impairment in the functionality of Bipolar Disorder Type I, even when euthymic (EutBDI). The aim of this study was to explore this relationship, taking functional outcome from a multidimensional point of view. An extended neuropsychological battery of executive tests and measures of social functioning were administered to 31 EutBDI and 25 non-psychiatric patients. Percentage of patients scoring lower than -1.64 SD was calculated for each executive measure. This was compared in terms of clinical features to those with normal performance. Partial correlations and ANCOVA were applied between psychosocial and executive variables within the EutBDI-group. Patients reached poorer scores in mental flexibility, plan implementing, set-shifting, and fluency (p<0.05). 76% of patients performed poorly on some of the executive tests, although only around 1/3 reached a clinical deficit (<-1.64SD). Executive functioning was related to some clinical, evolution, and treatment variables. A better use of leisure time, higher competence for independent living and holding a skilled type of profession were significantly associated with a better performance on planning, set-shifting, and fluency tasks.
Does a genome-wide screen for modifiers of transgene variegation identify genes with critical roles in development?	Some years ago we established an N-ethyl-N-nitrosourea screen for modifiers of transgene variegation in the mouse and a preliminary description of the first six mutant lines, named MommeD1-D6, has been published. We have reported the underlying genes in three cases: MommeD1 is a mutation in SMC hinge domain containing 1 (Smchd1), a novel modifier of epigenetic gene silencing; MommeD2 is a mutation in DNA methyltransferase 1 (Dnmt1); and MommeD4 is a mutation in Smarca 5 (Snf2h), a known chromatin remodeler. The identification of Dnmt1 and Smarca5 attest to the effectiveness of the screen design. We have now extended the screen and have identified four new modifiers, MommeD7-D10. Here we show that all ten MommeDs link to unique sites in the genome, that homozygosity for the mutations is associated with severe developmental abnormalities and that heterozygosity results in phenotypic abnormalities and reduced reproductive fitness in some cases. In addition, we have now identified the underlying genes for MommeD5 and MommeD10. MommeD5 is a mutation in Hdac1, which encodes histone deacetylase 1, and MommeD10 is a mutation in Baz1b (also known as Williams syndrome transcription factor), which encodes a transcription factor containing a PHD-type zinc finger and a bromodomain. We show that reduction in the level of Baz1b in the mouse results in craniofacial features reminiscent of Williams syndrome.	Cholecystokinin (CCK) and gastrin are related gastrointestinal hormones with documented cardiovascular effects of exogenous administration. It is unknown whether measurement of endogenous CCK or gastrin in plasma contains information regarding cardiovascular mortality. Mortality risk was evaluated using Cox proportional hazard regression and Kaplan-Meier analyses. Elderly patients in a primary care setting with symptoms of cardiac disease, i.e. shortness of breath, peripheral edema, and/or fatigue, were evaluated (n=470). Primary care patients were followed for 13years (from 1999); the 5-year all-cause and cardiovascular mortality was used as end point. In univariate analysis, patients in the 4th CCK quartile had an increased risk of 5-year cardiovascular mortality (hazard ratio 3.9, 95% confidence interval: 2.1-7.0, p<0.0001). In multivariate analysis including established factors associated with cardiovascular mortality, CCK concentrations in the 4th quartile were still associated with increased 5-year cardiovascular mortality risk (HR 3.1, 95% C.I.: 1.7-5.7, p=0.0004), even when including 4th quartile NT-proBNP concentrations in the same model. We observed a marked difference between the genders, where CCK concentrations in the 4th quartile were associated with a higher 5-year cardiovascular mortality in female patients (HR 8.99, 95% C.I.: 3.49-102.82, p=0.0007) compared to men (1.47, 95% C.I.: 0.7-3.3, p=0.35). In contrast, no significant information was obtained from 4th quartile gastrin concentrations on 5-year cardiovascular mortality risk.
Do [ Application of vital dye CFDA-SE and SNARF-1 to evaluate mixed lymphocyte reaction ]?	To establish a new method for more comprehensive evaluation of responsive intensity in one-way mixed lymphocyte reaction (MLR). CFDA-SE labeled lymphocytes from lymph nodes of BALB/cJ mice were applied as responder cells, and SNARF-1 labeled splenocytes from BALB/cJ or C57BL/6 mice which had been pretreated with mitomycin C were applied as stimulator cells to establish mixed lymphocyte culture (MLC). After 96 h of culture, cells were harvested and analyzed by flow cytometry to acquire the proliferative information of SNARF-1 negative and CFSE positive staining responder cells. ModFit software was then used to get more proliferation related index. With increasing division cycles, the CFSE fluorescence was diluted to the extent that the responder cells could not be discriminated from stimulator cells, which was resolved by gating SNARF-1 positive cells out to define responder cells. Several important proliferation related indexes were obtained by ModFit software, such as precursor frequency and proliferation index, etc.	Two recent genome-wide association studies identified the liver expressed transmembrane protein adiponutrin to be associated with liver related phenotypes such as non-alcoholic fatty liver disease and liver function enzymes. These associations were not uniformly reported for various ethnicities. The aim of this study was to investigate a common non-synonymous variant within adiponutrin (rs738409, exon 3) with parameters of liver function in three independent West Eurasian study populations including a total of 4290 participants. The study was performed in (1) the population based Bruneck Study (n=783), (2) the Salzburg Atherosclerosis Prevention Program in Subjects at High Individual Risk Study from Austria based on a healthy working population (n=1705), and the Utah Obesity Case-Control Study including a group of 1019 severely obese individuals (average body mass index 46.0 kg/m(2)) and 783 controls from the same geographical region of Utah. Liver enzymes measured were alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyl transferase (GGT). A strong recessive association of this polymorphism was found with age and gender adjusted ALT and AST concentrations: being homozygous for the minor allele resulted in a highly significant increase of ALT concentration of 3.53 U/l (p=1.86 x 10(-9)) and of AST concentration of 2.07 U/l (p=9.58 x 10(-6)), respectively. The associations were consistently found in all three study populations.
Does the tissue Doppler imaging derived post-systolic velocity notch originate at the aortic annulus?	A distinct velocity pattern represented by a "notch" is observed during the time interval between the end of the systolic and the onset of the early diastolic velocity wave on longitudinal myocardial velocity curve. The origin of the post-systolic velocity notch (PSN) has not been resolved. The high frame rate color tissue Doppler imaging of the apical longitudinal axis was performed in 32 healthy subjects. The time delays of the PSN onset at the posterior aortic wall (AW), the mid anteroseptal wall (MAS) and the posterior mitral annulus (MA) relatively to the anterior aortic annulus (AA) were found to be significantly longer than zero (5.1 ± 2.2, 6.0 ± 2.3, 6.8 ± 2.8 ms; p < 0.001). The amplitude was the highest at the AA when compared to the AW, the MAS and the MA (4.77 ± 1.28 vs. 2.88 ± 1.11, 2.15 ± 0.73, 2.44 ± 1.17 cm/s; p < 0.001). A second PSN spike was identifiable in 10/32 (31%) of the studied subjects at the AA. Of these, 9 (28%) exhibited a second PSN spike at the AW, 3 (9%) at the MAS and no one at the MA.	Chronic rhinosinusitis without nasal polyps (CRSsNP) and with nasal polyps (CRSwNP) is characterized by persistent inflammation of sinonasal mucosa. Glucocorticoid-induced leucine zipper (GILZ) is a recently described anti-inflammatory mediator. Here we analysed the expression of GILZ in CRSsNP and CRSwNP, its association with response to surgery, and its cytokine-driven expression regulation in the upper airways. Methods The messenger RNA (mRNA) and protein expression of GILZ in 33 CRSsNP, 32 CRSwNP, and 11 control samples was assessed by means of a quantitative RT-PCR and immunohistochemistry, respectively. Nasal explant culture was used to investigate the effect of IFN-gamma, IL-4, IL-13, IL-1beta, and TNF-alpha on GILZ mRNA expression in normal sinonasal mucosa. The GILZ mRNA and protein expression was significantly suppressed in both CRSsNP and CRSwNP patients compared with controls. No significant difference in GILZ expression was found between CRSsNP and CRSwNP patients. Comparing patients responsive and patients recalcitrant to surgery, a significant further decrease of GILZ expression was found in recalcitrant patients both in the CRSsNP and in the CRSwNP group. IL-1beta, TNF-alpha, IL-4, and IL-13 reduced, whereas IFN-gamma enhanced GILZ mRNA levels in the sinonasal mucosa.
Is gATA5 and endothelial nitric oxide synthase expression in the ascending aorta related to aortic size and valve morphology?	The pathogenesis of aortic dilatation in patients with congenital aortic valve anomalies is poorly understood. Recent studies suggest that alterations of gene expression may be related to ascending aortic aneurysm formation in these patients. Knockout of endothelial nitric oxide synthase (eNOS) and GATA5 is associated with bicuspid aortic valves in mice. To study the role of eNOS and GATA5 in human congenital aortic valve disease and aortic dilatation, we investigated their gene expression in aortic tissue from patients with unicuspid, bicuspid, and tricuspid aortic valves. Samples from 84 patients (33 tricuspid, 32 bicuspid, and 19 unicuspid) were harvested intraoperatively from the ascending aorta. GATA5 and eNOS expression was determined by real-time polymerase chain reaction. GATA5 and eNOS expression in the aortic wall from patients with unicuspid aortic valves (GATA5: mean [M], 2.14; standard deviation [SD], 1.72; eNOS: M, 3.40; SD, 3.83) was significantly higher than in tricuspid aortic valves (GATA5: M, 1.12; SD, 0.80; eNOS: M, 1.00; SD, 0.74; each p < 0.05). Patients with bicuspid aortic valves (GATA5: M, 1.29, SD, 1.33; eNOS: M, 1.66; SD, 1.31) had a significantly higher eNOS expression than patients with tricuspid aortic valves (p < 0.05). The expression levels of eNOS and GATA5 correlated positively with each other and negatively with the ascending aortic diameter.	Symptom assessment by computers is only effective if it provides valid results and is perceived as useful for clinical use by the end users: patients and health care providers. To identify factors associated with discontinuation, time expenditure, and patient preferences of the computerized symptom assessment used in an international multicenter data collection project: the European Palliative Care Research Collaborative-Computerized Symptom Assessment. Cancer patients with incurable metastatic or locally advanced disease were recruited from 17 centers in eight countries, providing 1017 records for analyses. Observer-based registrations and patient-reported measures on pain, depression, and physical function were entered on touch screen laptop computers. The entire assessment was completed by 94.9% (n = 965), with median age 63 years (range 18-91 years) and median Karnofsky Performance Status (KPS) score of 70 (range 20-100). Predictive factors for noncompletion were higher age, lower KPS, and more pain (P ≤ 0.012). Time expenditure among completers increased with higher age, male gender, Norwegian nationality, number of comorbidities, and lower physical functioning (P ≤ 0.007) but was inversely related to pain levels and tiredness (P ≤ 0.03). Need for assistance was predicted by higher age, nationality other than Norwegian, lower KPS, and lower educational level (P < 0.001). More than 50% of patients preferred computerized assessment to a paper and pencil version.
Does intrauterine growth restriction modify gene expression profiling in cord blood?	Small-for-gestational-age (SGA) newborns are at an increased risk for perinatal morbidity and mortality and development of metabolic syndromes such as cardiovascular disease and type 2 diabetes mellitus (T2DM) in adulthood. The mechanism underlying this increased risk remains unclear. In this study, genetic modifications of cord blood were investigated to characterize fetal change in SGA newborns. Gene expression in cord blood cells was compared between 10 SGA newborns and 10 appropriate-for-gestational-age (AGA) newborns using microarray analysis. Pathway analysis was conducted using the Ingenuity Pathways Knowledge Base. To confirm the microarray analysis results, quantitative real-time polymerase chain reaction (RT-PCR) was performed for upregulated genes in SGA newborns. In total, 775 upregulated and 936 downregulated probes were identified in SGA newborns and compared with those in AGA newborns. Of these probes, 1149 were annotated. Most of these genes have been implicated in the development of cardiovascular disease and T2DM. There was good agreement between the RT-PCR and microarray analyses results.	To study the long-term effects of selegiline in monotherapy and in combination with levodopa in the early phase of Parkinson disease (PD). One hundred fifty-seven de novo PD patients were randomized in a double-blind, placebo-controlled study of 7 years' duration. In the monotherapy part, selegiline significantly delayed the initiation of levodopa therapy vs placebo. The authors now report the results from the combination part of the study, in which 140 patients received selegiline or placebo in addition to individually tailored levodopa therapy. Compared with placebo, selegiline slowed the progression of disease disability as measured by the Unified Parkinson Disease Rating Scale (UPDRS) total score (p = 0.003) or by motor (p = 0.002) and Activities of Daily Living (p = 0.0002) subscores. After 5 years in combination therapy, the mean difference in the UPDRS total score was nearly 10 points, with patients receiving placebo having 35% higher scores. Simultaneously, patients receiving placebo needed progressively higher doses of levodopa than patients receiving selegiline; after 5 years, the mean dosage of levodopa was 19% higher with placebo than with selegiline (p = 0.0002). Considering the entire (monotherapy and combination therapy) 7-year study time, there was a trend for selegiline to delay the start of wearing-off fluctuations (hazard ratio 0.55, p = 0.08). In both phases of the study, selegiline was safe and well tolerated.
Does rat Kupffer cell-derived nitric oxide modulate induction of lymphokine-activated killer cell?	Nitric oxide is now recognized to regulate immune responses and cell viability in various organs. The present study was designed to clarify whether NO released from Kupffer cells modulates the lymphokine-activated killer (LAK) activity of interleukin 2 (IL-2)-treated splenocytes. Splenocytes and Kupffer cells were isolated from male Wistar rats and cocultured for 48 hours in the presence of lipopolysaccharide (1 microgram/mL). The splenocyte LAK activity and expression of IL-2 receptor were determined. Kupffer cells with lipopolysaccharide reduced the IL-2 receptor expression and LAK activity of splenocytes. The addition of either NG-monomethyl-L-arginine, an inhibitor of NO synthesis, or aminoguanidine, an inhibitor of inducible NO synthase, to the medium reversed the suppression of IL-2 receptor expression and LAK activity by lipopolysaccharide-stimulated Kupffer cells. 8-bromoguanosine 3',5'-cyclic monophosphate and NO donors decreased the splenocyte LAK activity and IL-2 receptor expression. Treatment with lipopolysaccharide increased the inducible NO synthase activity as well as the nitrite and nitrate levels in the culture medium of Kupffer cells but not in splenocytes.	Prostate cancer (PCa) molecular subtypes have been defined by essentially mutually exclusive events, including ETS gene fusions (most commonly involving ERG) and SPINK1 overexpression. Clinical assessment may aid in disease stratification, complementing available prognostic tests. To determine the analytical validity and clinicopatholgic associations of microarray-based molecular subtyping. We analyzed Affymetrix GeneChip expression profiles for 1577 patients from eight radical prostatectomy cohorts, including 1351 cases assessed using the Decipher prognostic assay (GenomeDx Biosciences, San Diego, CA, USA) performed in a laboratory with Clinical Laboratory Improvements Amendment certification. A microarray-based (m-) random forest ERG classification model was trained and validated. Outlier expression analysis was used to predict other mutually exclusive non-ERG ETS gene rearrangements (ETS(+)) or SPINK1 overexpression (SPINK1(+)). Associations with clinical features and outcomes by multivariate logistic regression analysis and receiver operating curves.
Does dietary fiber enhance a tumor suppressor signaling pathway in the gut?	To determine whether sodium butyrate (NaB), a major short-chain fatty acid produced in the human gut by bacterial fermentation of dietary fiber, enhances transforming growth factor (TGF)-beta signaling and potentiates its tumor suppressor activity in the gut. The molecular mechanisms by which dietary fiber decreases the risk of colon cancers are poorly characterized. TGF-beta is an important tumor suppressor in the gut and has many similar biologic activities as NaB. Therefore, we hypothesized that the chemo-preventive effects of NaB are mediated in part by enhancing TGF-beta signaling and its tumor suppressor function in the gut. The effects of NaB on Smad3 expression in rat intestinal epithelial (RIE-1) cells and 6 human colon cancer cell lines were examined. The effects of NaB on TGF-beta-induced Smad3 phosphorylation and plasminogen activator inhibitor-1 (PAI-1) and cyclooxygenase-2 (COX-2) gene expression were also examined in RIE-1 cells. Finally, the effects of NaB and TGF-beta on anchorage-independent growth were examined in Akt-transformed RIE-1 cells. NaB induced Smad3 in RIE-1 cells and in 4 human colon cancer cell lines. NaB enhanced TGF-beta-induced Smad3 phosphorylation and potentiated TGF-beta-induced PAI-1 expression. NaB and TGF-beta synergistically inhibited anchorage-independent growth of Akt-transformed RIE-1 cells.	To find sensitive and specific laboratory examination items for early diagnosing and monitoring liver transplantation reject reaction. Randomly investigate 41 liver transplantation patients, among them there were 16 patients with reject reaction (including 12 with acute rejection, 4 with chronic rejection). Plasma soluble thrombomodulin (STM) and von Willebrand factor (vWF) levels were measured before operation and every other day after operation. Plasma STM level increased significantly after operation, two days before rejection and after acute rejection (5.58 ng/ml +/- 0.42 ng/ml, 5.93 ng/ml +/- 0.45 ng/ml, and 7.88 ng/ml +/- 0.29 ng/ml, respectively), so did vWF level (101.2% +/- 4.68%, 104.3% +/- 5.78%, and 127.7% +/- 5.74%, respectively). STM level was much higher in acute rejection than that in chronic rejection (7.88 ng/ml +/- 0.29 ng/ml vs. 6.35 ng/ml +/- 0.54 ng/ml, t = 2.46, P < 0.05), in no reaction group after impacting therapy than in effective group (8.30 ng/ml +/- 0.19 ng/ml vs. 3.82 ng/ml +/- 0.22 ng/ml, t = 12.98, P < 0.01), and in dead group after treatment than in living group (7.98 ng/ml +/- 0.18 ng/ml vs. 6.51 ng/ml +/- 0.41 ng/ml, t = 3.39, P < 0.01).
Does [ Removal of YY1 binding sites in HPV 16 LCR increase viral transforming activities on mouse fibroblasts ]?	To study the effect of removal of YY1 binding sites within the LCR region of HPV 16 on viral transforming activity. Previously we had generated new plasmids carrying HPV 16 whole genome, which contained naturally occurred mutated LCR sequences. The viral transforming abilities on mouse fibroblasts were evaluated in anchorage-independent assays, while the expression and activity of YY1 protein in fibroblasts were tested with EMSA and luciferase assays. YY1 protein was expressed in mouse fibroblasts C127, with ability for DNA binding and repression on P97 activity. Both HPV 16 wild-type DNA and mutated DNAs were transfected into C127 cells and spread to the soft-agarose mediums after selecting with G 418. The growth numbers of the cells transfected with mutated HPV 16 DNAs were 2-10 fold more than that with wild-type HPV 16 DNA.	The value of a new diagnostic test is usually established by analyzing its accuracy in relation to a reference standard. Here we describe a potentially better model of diagnostic research, namely, a diagnostic randomized clinical trial (D-RCT), and discuss its pros and cons using management of critical limb ischemia as an example. Patients clinically suspected of critical limb ischemia are randomized either for the conventional management strategy (treating physician determines the diagnostic and therapeutic strategy on clinical judgment and ankle pressure) or new strategy (transcutaneous oxygen and toe pressure determine the diagnostic and therapeutic strategy). The effect of the diagnostic work-up on the diagnostic and therapeutic process and clinical outcome will be evaluated. A D-RCT is suited when a true reference standard is lacking. It is the best available research method to control for confounding and bias, and it also incorporates the total effect (interpretation and side effects) on clinical outcome. The D-RCT has some disadvantages, however, as to the power and size of the trial and the influence of treatment on the outcome parameter.
Is serum gamma-glutamyltransferase associated with subclinical atherosclerosis in patients with type 2 diabetes?	This study investigated the association between serum gamma-glutamyltransferase (GGT) level and subclinical atherosclerosis in patients with type 2 diabetes. This cross-sectional study involved 1024 patients with type 2 diabetes mellitus. Measurement of brachial-ankle pulse wave velocity (baPWV; as a marker of arterial stiffness) and an ultrasound assessment of carotid atherosclerosis were performed. Subclinical atherosclerosis was defined by the presence of a high baPWV (≥1720 cm/s), carotid atherosclerosis (intima-media thickness >0.8 mm or the presence of plaques), and carotid stenosis (≥50 % of luminal narrowing). The subjects were stratified into quartiles according to GGT level, and the relationship between GGT level and subclinical atherosclerosis was analysed. Serum GGT levels were closely associated with obesity, atherogenic dyslipidemia, and metabolic syndrome. However, serum GGT levels did not show a linear association with baPWV, carotid intima-media thickness, or plaque grade. The prevalence of high baPWV, carotid atherosclerosis, and carotid stenosis did not differ between the quartiles in men and women. Multivariate logistic regression analyses revealed no association between GGT level and high baPWV, carotid atherosclerosis, and carotid stenosis, either as continuous variables or quartiles.	Medialization of the glenohumeral center of rotation alters the moment arm of the deltoid, can affect muscle function, and increases the risk for scapular notching due to impingement. The objective of this study was to determine the effect of position of the glenosphere on deltoid efficiency and the range of glenohumeral adduction. Scapulohumeral bone models were reconstructed from computed tomography scans and virtually implanted with primary or reverse total shoulder arthroplasty implants. The placement of the glenosphere was varied to simulate differing degrees of "medialization" and inferior placement relative to the glenoid. Muscle and joint forces were computed during shoulder abduction in OpenSim musculoskeletal modeling software. The average glenohumeral joint reaction forces for the primary total shoulder arthroplasty were within 5% of those previously reported in vivo. Superior placement or full lateralization of the glenosphere increased glenohumeral joint reaction forces by 10% and 18%, respectively, relative to the recommended reverse total shoulder arthroplasty position. The moment arm of the deltoid muscle was the highest at the recommended baseline surgical position. The baseline glenosphere position resulted in a glenohumeral adduction deficit averaging more than 10° that increased to more than 25° when the glenosphere was placed superiorly. Only with full lateralization was glenohumeral adduction unaffected by superoinferior placement.
Does aspirin improve early arterial patency after streptokinase treatment for acute myocardial infarction?	To investigate the hypothesis that the magnitude of the life saving effect of aspirin in the second international study of infarct survival (ISIS-2) trial cannot be explained solely by prevention of late reocclusion of the infarct related artery. The aim of this study was to discover whether or not aspirin in combination with streptokinase had an adjuvant thrombolytic effect. Aspirin (150 mg) or placebo was given at the start of streptokinase infusion to 200 patients seen within six hours of the start of prolonged ischaemic cardiac pain and ST segment elevation. All patients received active aspirin at three hours. Patency of the infarct related artery was assessed non-invasively by the normalised rise of creatine kinase activity at three hours after starting streptokinase in these 200 patients and in a further 52 patients who had already taken aspirin within one week of the start of infarction. Rise in creatine kinase activity from baseline to > or = 20% or < 20% of the peak rise of activity in blood taken at three hours after starting infusion of streptokinase. This correlates with patency or occlusion of the infarct related coronary artery at about 2.5 hours after starting streptokinase. Assessed in this way, patency of the infarct related artery was 60% in patients given aspirin, 63% in those given placebo, and 62% in patients who had already taken aspirin within one week of infarction.	Bacterial vaginosis is a risk factor for preterm birth. The various conventional methods for its diagnosis are laborious and not easily reproducible. Molecular quantification methods have been reported recently, but the specific risk factors they might identify remain unclear. A prospective multicenter national study included pregnant women at risk of preterm birth. A quantitative molecular tool using a specific real-time polymerase chain reaction assay and serial dilutions of a plasmid suspension quantified Atopobium vaginae, Gardnerella vaginalis, lactobacilli, Mycoplasma hominis, and the human albumin gene (for quality control). In 813 pregnancies, high vaginal loads of either or both of A. vaginae and G. vaginalis were associated with preterm birth (hazard ratio [HR], 3.9; 95% confidence interval {CI}, 1.1-14.1; P = .031). A high vaginal load of A. vaginae was significantly associated with shortened time to delivery and therefore pregnancy length. These times were, respectively, 152.2 and 188.2 days (HR, 5.6; 95% CI, 1.5-21.3; P < .001) before 22 weeks, 149.0 and 183.2 days (HR, 2.8; 95% CI, 1.1-8.2; P = .048) before 28 weeks, and 132.6 and 170.4 days (HR, 2.2; 95% CI, 1.1-4.6; P = .033) before 32 weeks. After multivariate analysis, A. vaginae levels ≥10(8) copies/mL remained significantly associated with delivery before 22 weeks of gestation (adjusted HR, 4.7; 95% CI, .2-17.6; P = .014).
Does cyclin I correlate with VEGFR-2 and cell proliferation in human epithelial ovarian cancer?	Ovarian cancer is the most lethal of all gynecologic malignancies. It is characterized by the spread of intraperitoneal tumors, accumulation of ascites, and formation of tumor blood vessels. Cyclin I has been linked with angiogenesis-related proteins, like vascular endothelial growth factor (VEGF) and VEGF receptor 2 (VEGFR-2), in human breast cancer. We examined whether an association exists between expression of cyclin I, VEGFR-2, clinicopathologic parameters and survival of patients with epithelial ovarian cancer (EOC). Cyclin I and VEGFR-2 expressions were analyzed by immunohistochemistry in 55 human primary EOC tissue specimens. Cyclin I immunoreactivity was significantly correlated with VEGFR-2 (R=0.4587, P=0.0004), and immunolabeling of cyclin I and VEGFR-2 significantly correlated with cancer cells' proliferative activity evaluated using cyclin A labeling index as a marker (R=0.3107, P=0.0209 and R=0.4183, P=0.0015, respectively). VEGFR-2 immunostaining was significantly higher in advanced, poorly differentiated, and suboptimally resected EOCs compared to their counterparts (P<0.05). Finally, higher VEGFR-2 expression was significantly associated with shorter disease-free survival (P=0.0437).	To evaluate the immediate effects of indirect moxibustion, a traditional local thermal therapy, on renal hemodynamics by using Doppler ultrasonography (US). Prospective observational study of postintervention changes in several variables. Gifu University Hospital, Gifu, Japan. Eleven healthy persons (7 men and 4 women; mean age±standard deviation, 32.6±5.7 years) were enrolled. Indirect moxibustion was applied for 4 minutes to bilateral lower back acupuncture points (BL23). Each participant received 3 successive treatments. The main outcome measurement was resistive index (RI) in the renal segmental arteries. Blood flow variables, including RI, were measured for 6 renal segmental arteries by Doppler US at rest (baseline), immediately after completion of moxibustion (post 1), and 10 minutes later (post 2). Participants were monitored for adverse events during the intervention. The mean RI was 0.578±0.037 at baseline, 0.546±0.027 at post 1, and 0.547±0.032 at post 2. RI decreased significantly between post 1 and baseline (95% confidence interval [CI], -0.053 to -0.011; p=0.003) and between post 2 and baseline (95% CI, -0.052 to -0.009; p=0.005). No adverse events, such as burns, were observed.
Does dehydration affect spinal cord cross-sectional area measurement on MRI in healthy subjects?	This was a prospective cohort observational study. To determine the effect of dehydration and rehydration on spinal cord cross-sectional area (CSA) measurement on magnetic resonance imaging (MRI). MRI Research Centre, University of British Columbia, Canada. Ten healthy subjects (aged 21-32 years) were scanned on a 3T MRI scanner at four time points: (1) baseline, (2) rescan after 1 h, (3) the next day after fasting for a minimum of 14 h and (4) after rehydration with 1.5 l of water over the course of 1 h. Two independent, established semi-automatic CSA measurement techniques (one based on two-dimensional (2D) edge detection, the other on three-dimensional (3D) surface fitting) were applied to a 3D T1-weighted scan of each subject at each time point, with the operator blinded to scan order. The percentage change in CSA from baseline to each subsequent time point was calculated. One-tailed paired t-tests were used to assess the significance of the changes from baseline. A decrease in CSA following dehydration was detected by both measurement methods, with a mean change of -0.654% (s.d.=0.778, P<0.05) and -0.650% (s.d.=1.071, P<0.05) for the first and second methods, respectively.	Atmospheric pollution may play a role in the immune response to allergens either directly or by entering the food chain. While particulate platinum group elements (PLGE) emitted by catalytic converters can be considered biologically inert, approximately 10% of these species accumulate in the environment as bioavailable soluble forms. We challenged in vitro human immature and mature monocyte-derived dendritic cells with subtoxic concentrations of soluble species of PLGE. Dendritic cells were studied both at baseline and following treatment with Na(2)PtCl(6), Na(2)PdCl(6) or Na(3)RhCl(6). (NH(4))(6)Mo(7)O(24) was included as control. The following end-points were considered: expression of differentiation markers, effectiveness of allergen presentation and Th2 cytokine production by cocultured T lymphocytes, expression of IgE-type I receptor and efficiency of IgE-dependent endocytosis. We found that treatment with PLGE (but not with the control metal) increased costimulatory molecule expression and antigen presentation, amplified IL-5 production by cocultured T lymphocytes, upregulated IgE-type I receptor membrane expression, and augmented IgE-type I receptor-mediated endocytosis.
Is activation of neutral sphingomyelinase involved in acute hypoxic pulmonary vasoconstriction?	The mechanisms involved in hypoxic pulmonary vasoconstriction (HPV) are not yet fully defined. The aim of the study was to determine the role of protein kinase C zeta (PKCzeta) and neutral sphingomyelinase (nSMase) in HPV. Ceramide content was measured by immunocytochemistry and voltage-gated potassium channel (KV) currents were recorded by the patch clamp technique in isolated rat pulmonary artery smooth muscle cells (PASMC). Contractile responses were analysed in rat pulmonary arteries mounted in a wire myograph. Pulmonary pressure was recorded in anesthetized open-chest rats. Protein and mRNA expression were measured by western blot and RT-PCR, respectively. We found that hypoxia increased ceramide content in PASMC which was abrogated by inhibition of nSMase, but not acid sphingomyelinase (aSMase). The hypoxia-induced vasoconstrictor response in isolated pulmonary arteries and the inhibition of KV currents were strongly reduced by inhibition of PKCzeta or nSMase but not aSMase. The nSMase inhibitor GW4869 prevented HPV in vivo. The vasoconstrictor response to hypoxia was mimicked by exogenous addition of bacterial Smase and ceramide. nSMase2 mRNA expression was approximately 10-fold higher in pulmonary compared with mesenteric arteries. In mesenteric arteries, hypoxia failed to increase ceramide but exogenous SMase induced a contractile response.	Bariatric surgery not only elicits weight loss but also rapidly resolves diabetes. However, the mechanisms remain unclear. The present study investigates how diabetes and liver steatosis are improved after duodenal-jejunal bypass (DJB) compared with a glucagon-like peptide-1 (GLP-1) analog and correlations between bile acids and GLP-1 secretion. We initially determined the effects of bile acids on GLP-1 in vitro and then assigned 12 male 16-week-old Otsuka Long-Evans Tokushima Fatty rats to groups that underwent DJB, a sham operation, or were treated with the GLP-1 receptor agonist, liraglutide (n = 4 each). Blood glucose, insulin, GLP-1, serum bile acids, liver steatosis, and the number of GLP-1 positive cells (L cells) in the small intestine and colon were investigated in the three groups at eight weeks postoperatively. Levels of GLP-1mRNA were upregulated and GLP-1 secretion increased in cells incubated with bile acids in vitro. Weight gain was suppressed more in the DJB than in the sham group in vivo. Diabetes was more improved and GLP-1 levels were significantly higher in the DJB than in the sham group. Serum bile acids were significantly increased, the number of L cells in the ileum was upregulated compared with the sham group, and liver steatosis was significantly improved in the DJB compared with the other two groups.
Does voxel-based morphometry reveal extra-nigral atrophy patterns associated with dopamine refractory cognitive and motor impairment in parkinsonism?	To determine overall patterns of brain atrophy associated with memory, executive function (EF) and dopamine non-responsive motor measures in older parkinsonian patients. Forty-three older PD patients (>or=65 years) and matched controls underwent a neurological examination (Unified Parkinson's Disease Rating Scale, separated into dopamine responsive and dopamine non-responsive signs) and neuropsychological testing (memory: California Verbal Learning Test (CVLT)) and a composite of index of executive function (EF): Stroop Interference, Trail Making Test Part B, and digit ordering. All underwent volumetric MRI scans analyzed using voxel-based morphometry (VBM). Group comparisons, and the correlations between MRI gray and white matter volume and motor and cognitive measures were controlled for age, sex and intracranial volume. Cerebellar volume was independently measured using a validated extraction method. Patients and controls were matched for demographics and global cognitive measures. VBM indicated significant gray matter (GM) atrophy in the cerebellum in PD and was confirmed independently. Poor memory was associated with GM atrophy in the left (uncus, middle temporal and fusiform gyri) and right temporal lobes and left putamen. Dopamine non-responsive motor signs and EF were associated with caudate atrophy. EF was also associated with GM atrophy in the middle temporal gyri, the left precuneus and cerebellum.	The generation of inflammatory mediators from monocytes activated by HLA Class II antibodies is thought to play important roles in the etiology of nonhemolytic transfusion reactions. Increased permeability of endothelial cells contributes to the pathogenesis of rash, urticaria, angioedema, and pulmonary edema, which are symptoms of transfusion reactions. We investigated whether inflammatory mediators released from monocytes upon stimulation by HLA Class II antibodies could increase endothelial permeability. Human endothelial cell monolayers were incubated with cell-free supernatants of peripheral blood mononuclear cells (PBMNCs) stimulated with HLA Class II antibody-containing plasma (anti-HLA-DR plasma), which has been implicated in severe nonhemolytic transfusion reactions. The permeability of endothelial cells to dextran was measured. The supernatants of PBMNCs stimulated with the anti-HLA-DR plasma in corresponding antigen-antibody combinations were able to increase endothelial permeability. At least 3 hours of exposure of PBMNCs to anti-HLA-DR plasma was required to produce a supernatant that could induce a significant increase in permeability. Simultaneous addition of tumor necrosis factor alpha (TNF-alpha) and interleukin 1 beta (IL-1 beta) neutralizing antibodies to the activated PBMNC supernatant significantly reduced the increase in permeability. Treatment of the endothelial cells with an inhibitor of nuclear factor kappaB (NF-kappaB), but not inhibitors of apoptosis, significantly prevented the increase in permeability.
Is initiation of nutritional support delayed in critically ill obese patients : a multicenter cohort study?	A high catabolic rate characterizes the acute phase of critical illness. Guidelines recommend an early nutritional support, regardless of the previous nutritional status. We aimed to assess whether the nutritional status of patients, which was defined by the body mass index (BMI) at admission in an intensive care unit (ICU), affected the time of nutritional support initiation. We conducted a cohort study that reported a retrospective analysis of a multicenter ICU database (OUTCOMEREA) by using data prospectively entered from January 1997 to October 2012. Patients who needed orotracheal intubation within the first 72 h and >3 d were included. Data from 3257 ICU stays were analyzed. The delay before feeding was different according to BMI groups (P = 0.035). The delay was longer in obese patients [BMI (in kg/m²) ≥30; n = 663] than in other patients with either low weight (BMI <20; n = 501), normal weight (BMI ≥20 and <25; n = 1135), or overweight (BMI ≥25 and <30; n = 958). The association between nutritional status and a delay in nutrition initiation was independent of potential confounding factors such as age, sex, and diabetes or other chronic diseases. In comparison with normal weight, the adjusted RR (95% CI) associated with a delayed nutrition initiation was 0.92 (0.86, 0.98) for patients with low weight, 1.00 (0.94, 1.05) for overweight patients, and 1.06 (1.00, 1.12) for obese patients (P = 0.004).	Subcortical band heterotopia (SBH, or double cortex syndrome) is a neuronal migration disorder consisting of heterotopic bands of gray matter located between the cortex and the ventricular surface, with or without concomitant pachygyria. Most cases show diffuse or anteriorly predominant (A>P) migration abnormality. All familial and 53% to 84% of sporadic cases with diffuse or A>P SBH harbor a mutation of the DCX gene, leaving the genetic causes unexplained, and genetic counseling problematic, in the remaining patients. Our purpose was to verify the extent to which exonic deletions or duplications of the DCX gene would account for sporadic SBH with A>P gradient but normal gene sequencing. We identified 23 patients (22 women, 1 man) with sporadic, diffuse, or anteriorly predominant SBH. After sequencing the DCX gene and finding mutations in 12 (11 women, 1 man), we used multiplex ligation-dependent probe amplification (MLPA) to search for whole-exon deletions or duplications in the 11 remaining women. We used semiquantitative fluorescent multiplex PCR (SQF-PCR) and Southern blot to confirm MLPA findings. MLPA assay uncovered two deletions encompassing exons 3 to 5, and one involving exon 6, in 3 of 11 women (27%) and raised the percentage of DCX mutations from 52% to 65% in our series. SQF-PCR performed in all three women and Southern blot analysis performed in two confirmed the deletions.
Does loss of Parp-1 affect gene expression profile in a genome-wide manner in ES cells and liver cells?	Many lines of evidence suggest that poly(ADP-ribose) polymerase-1 (Parp-1) is involved in transcriptional regulation of various genes as a coactivator or a corepressor by modulating chromatin structure. However, the impact of Parp-1-deficiency on the regulation of genome-wide gene expression has not been fully studied yet. We employed a microarray analysis covering 12,488 genes and ESTs using mouse Parp-1-deficient (Parp-1-/-) embryonic stem (ES) cell lines and the livers of Parp-1-/- mice and their wild-type (Parp-1+/+) counterparts. Here, we demonstrate that of the 9,907 genes analyzed, in Parp-1-/- ES cells, 9.6% showed altered gene expression. Of these, 6.3% and 3.3% of the genes were down- or up-regulated by 2-fold or greater, respectively, compared with Parp-1+/+ ES cells (p < 0.05). In the livers of Parp-1-/- mice, of the 12,353 genes that were analyzed, 2.0% or 1.3% were down- and up-regulated, respectively (p < 0.05). Notably, the number of down-regulated genes was higher in both ES cells and livers, than that of the up-regulated genes. The genes that showed altered expression in ES cells or in the livers are ascribed to various cellular processes, including metabolism, signal transduction, cell cycle control and transcription. We also observed expression of the genes involved in the pathway of extraembryonic tissue development is augmented in Parp-1-/- ES cells, including H19. After withdrawal of leukemia inhibitory factor, expression of H19 as well as other trophoblast marker genes were further up-regulated in Parp-1-/- ES cells compared to Parp-1+/+ ES cells.	To explore the implication of serial coronary changes on the late coronary outcomes in patients with Kawasaki disease (KD) with coronary aneurysms ≧ 4 mm. We performed a retrospective review of 78 patients with KD with large coronary aneurysms (1980-2013, male: 76.9%; 792 patient-years). Progressive coronary dilatation was defined for those with progressive enlargement of coronary arteries in 3 consecutive echocardiograms. We studied 27 patients with KD with giant aneurysms (≧ 8 mm) and 51 patients with KD with medium aneurysms (4-8 mm). All the giant and 43.1% of medium aneurysms persisted during the study period. For the patients with giant aneurysms, their 10-year freedom from acute myocardial infarction/cardiovascular death and all ischemia was 66% and 52%, respectively. The median intervals for the aneurysm diameters reaching their peak were 3.3 months (giant) and 0.25 months (medium), respectively. In patients with giant aneurysms, the 10-year freedom from ischemia was much lower in those with progressive coronary dilatation (28% vs 59%, P = .021). In patients with medium aneurysms, the probability of 5-year persistence of aneurysm was much greater (67.2% vs 14.8%, P < 10(-3)) in those with progressive coronary dilatation. Male sex and intravenous immunoglobulin therapy were not associated with the late outcomes in the patients with KD who had aneurysms larger than 4 mm.
Does passive resistance increase differentially in various jaw displacement directions?	In the present study, the passive resistance of the human jaw system was quantified in relation to the three-dimensional jaw displacement and the Posselt-envelope, using both in vivo measurements and computer simulation. In eight subjects, the jaw was passively displaced with a step-wise increasing force in three orthogonal directions. Muscle relaxation was monitored using electromyography (EMG) with visual feedback. A biomechanical model of an average human system was used to examine the contributions of the jaw muscles. The largest excursion was found for the vertical direction. Protrusive and lateral directions were more restricted. In protrusive and lateral directions, the jaw could generally move beyond the Posselt-envelope. The stiffness of the jaw increased with proceeding jaw displacement in all directions. The stiffness was larger in the protrusive direction than in the vertical and lateral directions. The model's predictions of stiffness were comparable to the in vivo measurements. However, in protrusive direction, the maximum jaw displacement was larger than in vivo. The estimated passive muscle forces showed that vertical displacement was mainly restricted by the complete group of closing muscles, while protrusive and lateral jaw displacement was restricted by selective individual muscles.	Most patients with hepatocellular carcinoma (HCC) present at advanced stages. The prevalence and clinical impact of delays during diagnostic evaluation among patients with HCC is unclear. To identify and characterize factors associated with diagnostic delays among patients with HCC. Records were reviewed for consecutive patients with cirrhosis and HCC at a large urban hospital between January 2005 and July 2012. Time from presentation to diagnosis was determined using Kaplan-Meier analysis. Diagnostic delay was defined as time to diagnosis exceeding 3 months, and multivariate logistic regression was used to identify correlates of diagnostic delays. Among 457 patients with HCC, 226 (49.5%) were diagnosed as outpatients. Among these, median time-to-diagnosis was 2.2 months, with 87 patients (38.5%) experiencing a diagnostic delay. Diagnostic delays were positively associated with the presence of hepatic encephalopathy (odds ratio [OR], 2.29; 95% CI, 1.03-5.07) and negatively associated with presentation after implementation of the electronic medical records (EMR) (OR, 0.28; 95% CI, 0.15-0.52) and presentation with an abnormal ultrasound (OR, 0.36; 95% CI, 0.19-0.67) on multivariate analysis. Higher rates of diagnostic delays were observed among those with hepatic encephalopathy (56% vs 35%), whereas lower rates were seen in those who presented after EMR implementation (26% vs 60%) and those who presented with an abnormal ultrasound with or without an elevated alpha fetoprotein level (27% vs 50%). Among 49 patients with mass-forming HCC and diagnostic delay, 18% had interval tumor growth of 2 cm or greater.
Is the apoB/apoA-I ratio better than the cholesterol ratios to estimate the balance between plasma proatherogenic and antiatherogenic lipoproteins and to predict coronary risk?	The apolipoprotein B (apoB)/apoA-I ratio represents the balance of proatherogenic and antiatherogenic lipoproteins. The purpose of this study was to determine whether the apoB/apoA-I ratio was superior to any of the cholesterol ratios - total cholesterol/high-density lipoprotein cholesterol (TC/HDL-C), low-density lipoprotein cholesterol (LDL-C)/HDL-C and non-HDL-C/HDL-C - in predicting the risk of coronary disease. Moreover, we examined whether any lipids, lipoproteins or cholesterol ratios add significant predictive information beyond that provided by the apoB/apoA-I ratio. Plasma lipids, lipoproteins, apoB, and apoA-I were measured in 69,030 men and 57,168 women above 40 years of age. After a mean follow-up of 98 months, 1183 men and 560 women had died from a myocardial infarction in this prospective apolipoprotein-related mortality risk (AMORIS) study. High apoB and a high apoB/apoA-I ratio were strongly related to increased coronary risk, while high apoA-I was inversely related to risk. The apoB/apoA-I ratio was superior to any of the cholesterol ratios in predicting risk. This advantage was most pronounced in subjects with LDL-C levels <3.6 mmol/l. Addition of lipids, lipoproteins or any cholesterol ratio to apoB/apoA-I in risk models did not further improve the strong predictive value of apoB/apoA-I.	CXC chemokines are induced by inflammatory stimuli in epithelial cells and some, like MIG/CXCL9, IP-10/CXCL10 and I-TAC/CXCL11, are antibacterial for Streptococcus pyogenes. SpeB from S. pyogenes degrades a wide range of chemokines (i.e. IP10/CXCL10, I-TAC/CXCL11, PF4/CXCL4, GROalpha/CXCL1, GRObeta/CXCL2, GROgamma/CXCL3, ENA78/CXCL5, GCP-2/CXCL6, NAP-2/CXCL7, SDF-1/CXCL12, BCA-1/CXCL13, BRAK/CXCL14, SRPSOX/CXCL16, MIP-3alpha/CCL20, Lymphotactin/XCL1, and Fractalkine/CX3CL1), has no activity on IL-8/CXCL8 and RANTES/CCL5, partly degrades SRPSOX/CXCL16 and MIP-3alpha/CCL20, and releases a 6 kDa CXCL9 fragment. CXCL10 and CXCL11 loose receptor activating and antibacterial activities, while the CXCL9 fragment does not activate the receptor CXCR3 but retains its antibacterial activity.
Is environmental lead exposure associated with visit-to-visit systolic blood pressure variability in the US adults?	The association between environmental lead exposure and blood pressure variability, an important risk factor for cardiovascular disease, is unexplored and unknown. The objective of the study was to test the hypothesis that lead exposure is associated with blood pressure variability. American participants 17 years of age or older from National Health and Nutrition Examination Survey III were included in the analysis. Participants' blood lead concentrations expressed as micrograms per deciliter were determined. The standard deviations of visit-to-visit systolic and diastolic blood pressure were calculated to determine blood pressure variability. Multivariable regression analyses adjusted for age, gender, race, smoking and socioeconomic status were employed. The participants' mean age and mean blood lead concentration were 42.72 years and 3.44 mcg/dl, respectively. Systolic blood pressure variability was significantly associated with environmental lead exposure after adjusting for the effect of the confounders. The unadjusted and adjusted means of visit-to-visit systolic blood pressure variability and the β coefficient of lead exposure were 3.44, 3.33 mcg/dl, β coefficient = 0.07, P < 0.01.	Bacterium-to-host signalling during infection is a complex process involving proteins, lipids and other diffusible signals that manipulate host cell biology for pathogen survival. Bacteria also release membrane vesicles (MV) that can carry a cargo of effector molecules directly into host cells. Supported by recent publications, we hypothesised that these MVs also associate with RNA, which may be directly involved in the modulation of the host response to infection. Using the uropathogenic Escherichia coli (UPEC) strain 536, we have isolated MVs and found they carry a range of RNA species. Density gradient centrifugation further fractionated and characterised the MV preparation and confirmed that the isolated RNA was associated with the highest particle and protein containing fractions. Using a new approach, RNA-sequencing of libraries derived from three different 'size' RNA populations (<50nt, 50-200nt and 200nt+) isolated from MVs has enabled us to now report the first example of a complete bacterial MV-RNA profile. These data show that MVs carry rRNA, tRNAs, other small RNAs as well as full-length protein coding mRNAs. Confocal microscopy visualised the delivery of lipid labelled MVs into cultured bladder epithelial cells and showed their RNA cargo labelled with 5-EU (5-ethynyl uridine), was transported into the host cell cytoplasm and nucleus. MV RNA uptake by the cells was confirmed by droplet digital RT-PCR of csrC. It was estimated that 1% of MV RNA cargo is delivered into cultured cells.
Is polymorphism of methylenetetrahydrofolate reductase gene ( C677T MTHFR ) a confounding factor of the relationship between serum uric acid level and the prevalence of hypertension in Japanese men?	The association between serum uric acid (UA) and the prevalence of hypertension, and the relationship between methylenetetrahydrofolate reductase (MTHFR) polymorphism and hypertension remains unclear. The aim of the present study was to investigate whether the C677T MTHFR mutation genotype (VV) is independently associated with the prevalence of hypertension or blood pressure (BP), and examined any interaction of MTHFR and UA with BP. Participants were randomly selected from all residents (aged 40-69 years) in a rural county of Japan, and the data for the men (n=335) were analyzed. ;Hypertension' was defined as systolic BP >or=140 and/or diastolic BP >or=90 mmHg and/or being administered antihypertensive medication. Serum UA level was independently associated with the prevalence of hypertension (odds ratio (95% confidence interval) =2.7 (1.2-5.9), p=0.047) for the highest tertile of serum UA (>or=398.5 micromol/L (6.7 mg/dl)) vs that of the lowest tertile (<321.2 micromol/L (5.4 mg/dl)), but the MTHFR mutation was not independently associated with prevalence of hypertension or BP. No interaction of the MTHFR mutation and serum UA with BP was found.	The more intensive sentinel node (SN) pathologic workup, the higher the SN-positivity rate. This is characterized by an increased detection of cases with minimal tumor burden (SUB-micrometastasis <0.1 mm), which represents different biology. The slides of positive SN from 3 major centers within the European Organization of Research and Treatment of Cancer (EORTC) Melanoma Group were reviewed and classified according to the Rotterdam Classification of SN Tumor Burden (<0.1 mm; 0.1-1 mm; >1 mm) maximum diameter of the largest metastasis. The predictive value for additional nodal metastases in the completion lymph node dissection (CLND) and disease outcome as disease-free survival (DFS) and overall survival (OS) was calculated. In 388 SN positive patients, with primary melanoma, median Breslow thickness was 4.00 mm; ulceration was present in 56%. Forty patients (10%) had metastases <0.1 mm. Additional nodal positivity was found in only 1 of 40 patients (3%). At a mean follow-up of 41 months, estimated OS at 5 years was 91% for metastasis <0.1 mm, 61% for 0.1 to 1.0 mm, and 51% for >1.0 mm (P < 0.001). SN tumor burden increased significantly with tumor thickness. When the cut-off value for SUB-micrometastases was taken at <0.2 mm (such as in breast cancer), the survival was 89%, and 10% had additional non-SN nodal positivity.
Is sero-reactivity to microbial components in Crohn 's disease associated with disease severity and progression , but not NOD2/CARD15 genotype?	Antibodies directed against the porin protein C of Escherichia coli (anti-OmpC) and Pseudomonas fluorescens (anti-I2) have recently been described in Crohn's disease (CD). Those directed against Saccharomyces cerevisiae (ASCA) and the perinuclear component of neutrophils (pANCA) have been more widely studied and may be of diagnostic importance. We aimed to assess the frequency of anti-OmpC, anti-I2, ASCA, and pANCA, in an independent Scottish CD cohort, establish phenotypic associations, and compare with a U.S. cohort. One hundred and forty-two well-characterized CD patients (76 females, median age 39 yr (17-88)) were studied. CD was classified by the Vienna classification. Sera were assayed for anti-OmpC, anti-I2, ASCA, and pANCA. Allele specific primers were used for NOD2/CARD15 genotyping. Anti-OmpC, anti-I2, ASCA, and pANCA were present in sera from 37%, 52%, 39%, and 14% of CD patients, respectively. Multivariate analysis demonstrated independent associations of anti-OmpC to be progression of disease type (p= 0.005) and long disease duration (p= 0.002), and those of anti-I2 to be long disease duration (p= 0.002) and the need for surgery (p= 0.033). ASCA were associated with disease progression (p < 0.001). When the presence and magnitude of all antibody responses were considered, reactivity to microbial components was associated with long disease duration (p < 0.001), progression of disease type (p < 0.001), penetrating disease (p= 0.008), small bowel disease (p < 0.02), and the need for surgery (p < 0.001). There was no association of antibody status to NOD2/CARD15 genotype.	To determine if central sympathetic blockade by dexmedetomidine, a selective alpha(2) adrenergic receptor agonist, prevents cardiac dysfunction associated with intracranial hypertension (ICH) in a rat model. Following intracisternal administration of dexmedetomidine (1 microg.microL(-1), 10 microL volume) or the stereoisomer levomedetomidine (1 microg.microL(-l), 10 microL volume) in halothane-anesthetized rats, a subdural balloon catheter was inflated for 60 sec to produce ICH. Intracranial pressure, hemodynamic, left ventricular (LV) pressures and electrocardiographic (ECG) changes were recorded. Plasma and myocardial catecholamines and malondialdehyde (MDA) levels were measured. After levomedetomidine administration, subdural balloon inflation precipitated an increase in mean arterial pressure (149 +/- 33% of baseline), heart rate (122 +/- 19% of baseline), LV systolic pressure (LVP), LV end-diastolic pressure (LVEDP), LV developed pressure (LVDP), LV dP/dtmax and rate pressure product (RPP) (132 +/- 19%, 260 +/- 142%, 119 +/- 15%, 126 +/- 24% and 146 +/- 33% of baseline value, respectively). ICH decelerated LVP fall (tau), as tau increased from 7.75 +/- 1.1 to 14.37 +/- 4.5 msec. Moreover, plasma norepinephrine levels were elevated (169 +/- 50% of baseline) and there was the appearance of cardiac dysrhythmias and other ECG abnormalities. This response was transient and cardiac function deteriorated in a temporal manner. Intracisternal dexmedetomidine prevented the rise in plasma norepinephrine, blocked the ECG abnormalities, and preserved cardiac function. Moreover, dexmedetomidine attenuated the rise in MDA levels.
Does tetrahydrocurcumin inhibit HT1080 cell migration and invasion via downregulation of MMPs and uPA?	Tetrahydrocurcumin (THC) is an active metabolite of curcumin. It has been reported to have similar pharmacological activity to curcumin. The proteases that participate in extracellular matrix (ECM) degradation are involved in cancer cell metastasis. The present study investigates the effect of an ultimate metabolite of curcumin, THC, on the invasion and motility of highly-metastatic HT1080 human fibrosarcoma cells. The effect of THC on HT1080 cell invasion and migration was determined using Boyden chamber assay. Cell-adhesion assay was used for examining the binding of cells to ECM molecules. Zymography assay was used to analyze the effect of THC on matrix metalloproteinase (MMP)-2, MMP-9, and urokinase plasminogen activator (uPA) secretion from HT1080 cells. Tissue inhibitor of metalloproteinase (TIMP)-2 and membrane-type 1 matrix metalloproteinase (MT1-MMP) proteins levels were analyzed by Western blotting. Treatment with THC reduced HT1080 cell invasion and migration in a dose-dependent manner. THC also decreased the cell adhesion to Matrigel and laminin-coated plates. Analysis by zymography demonstrated that treatment with THC reduced the levels of MMP-2, MMP-9, and uPA. THC also inhibited the levels of MT1-MMP and TIMP-2 proteins detected by Western blot analysis.	Child undernutrition and flooding are highly prevalent public health issues in Asia, yet epidemiological studies investigating this association are lacking. To investigate to what extent floods exacerbate poor nutritional status in children and identify most vulnerable groups, we conducted a population-based survey of children aged 6-59 months inhabiting flooded and non-flooded communities of the Jagatsinghpur district, Odisha (India), one year after large floods in 2008. Anthropometric measurements on 879 children and child, parental and household level variables were collected through face-to-face interviews in September 2009. The association between flooding and the prevalence of wasting, stunting and underweight was examined using weighted multivariate logistic regression for children inhabiting communities exposed solely to floods in 2008 and those communities repeatedly flooded (2006 and 2008) controlling for parental education and other relevant variables. We examined the influence of age on this association. Propensity score matching was conducted to test the robustness of our findings. The prevalence of wasting among children flooded in 2006 and 2008 was 51.6%, 41.4% in those flooded only in 2008, and 21.2% in children inhabiting non-flooded communities. Adjusting by confounders, the increased prevalence relative to non-flooded children in the exposed groups were 2.30 (adjusted prevalence ratio (aPR); 95% CI: 1.86, 2.85) and 1.94 (95% CI: 1.43, 2.63), respectively. Among repeatedly flooded communities, cases of severe wasting in children were 3.37 times more prevalent than for children inhabiting in those non-flooded (95% CI: 2.34, 4.86) and nearly twice more prevalent relative to those flooded only once. Those children younger than one year during previous floods in 2006 showed the largest difference in prevalence of wasting compared to their non-flooded counterparts (aPR: 4.01; 95% CI: 1.51, 10.63). RESULTS were robust to alternative adjusted models and in propensity score matching analyses. For similar analyses, no significant associations were found for child stunting, and more moderate effects were observed in the case of child underweight.
Is altered perineal microbiome associated with vulvovaginitis and urinary tract infection in preadolescent girls?	Vulvovaginitis has a known association with urinary tract infections (UTIs) in girls. We hypothesize that vulvovaginitis is a major contributor to UTIs in prepubertal girls by increasing periurethral colonization with uropathogens. Periurethral swabs and urine specimens were obtained from a total of 101 girls (58 with vulvovaginitis and 43 without vulvovaginitis). Specimens were cultured for bacterial growth. The dominant organism in the periurethral swabs and urine cultures was recorded and antibiotic sensitivity profiles were compared. Periurethral swabs from children with vulvovaginitis were associated with a statistically significant increase in uropathogenic bacteria (79% Enterococcus species or Escherichia coli) as the dominant culture compared with swabs from girls without vaginitis (18%) (p < 0.05). In children with vulvovaginitis, 52% of the urine cultures were positive for UTIs, and the dominant organism in the urine cultures matched the species and antibiotic sensitivity profile of the corresponding periurethral swab. Only 11% of the urine cultures from girls without vulvovaginitis were positive for UTIs.	To assess waiting time effect in patient with multiform glioblastoma (GBM) treated with 3D conformal planned postoperative radiotherapy and to investigate the impact of chemotherapy as first adjuvant treatment. We retrospectively analyzed 94 consecutive patients with histologically proven GBM. Surgery was considered as macroscopically complete in 33 cases (35%). Median irradiation dose was 60 Gy (8-63, mean 56 Gy). Dose per fractions was 1.8 Gy (five patients), 2 Gy (76 patients) and 2.7 Gy (13 patients). Forty patients received adjuvant pre-radiotherapy chemotherapy as intra-operative carmustine (nine patients) and adjuvant five-day protocol temozolomide alone (31 patients) or with cisplatinum (two patients). All patients received only one chemotherapy cycle. There were 56 males and 38 females. Median age was 62.1 years old (7-82, mean: 59.2 year). Median follow-up was nine months (1-49). For overall patients, median waiting time between fist clinical sign and start of the non surgical treatment was 68 days ((3-274, mean: 81.9 days). For those who received chemotherapy as first treatment, this waiting time was 54 days (3-221, mean 68.3 days). For overall patients, median waiting time between surgery and beginning of radiotherapy was 46 days (8-401, mean 59.3 days). For patients who did not receive chemotherapy as first adjuvant treatment this waiting time was 46 days (-278, mean 55.4 days). Median local control was 14.5 months. Six, 12-, 18-, and 24-month local control rates were 75.6+/-4.6%, 57.6+/-6.2%, and 36.7+/-8% and 27.6+/-8.2%, respectively. According to multivariate analysis, we retrieved two independent prognostic factors of local control, macroscopically total removal of the tumor [RR=2.85, IC 95% (1.3-6.5), p=0.012] and irradiation dose above 60 Gy, [RR=3.14, IC 95% (1.5-6.6), p=0.002]. Median overall survival was 14.3 months. Six-, 12-, 18, and 24-month overall survival rates were 84+/-3.9%, 55.1+/-5.9%, 34.2+/-6.3% and 30.4+/-6.7%, respectively. There was no independent prognostic factor.
Is global DNA hypomethylation associated with the development and poor prognosis of tongue squamous cell carcinoma?	Oral cancer is the 4th leading cause of cancer death for males and the top cancer in young adult males in Taiwan. Tongue squamous cell carcinoma (TSCC) is a common oral cancer and generally associated with poor prognosis. Global DNA hypomethylation at the 5 position of cytosine (5mC) is a well-known epigenetic feature of cancer. Therefore, the purpose of this study was to investigate the relationship of the global 5mC content with the tumorigenesis and prognosis of patients with TSCC. The levels of global 5mC were evaluated by immunohistochemistry using tissue microarray slides of 248 surgically resected TSCC and 202 corresponding tumor adjacent normal (TAN) tissues. We found that the level of 5mC in TSCC (P < 0.001) was significantly decreased as compared to TAN. Among TSCC tissues, decreased levels of 5mC were associated with female gender (P = 0.036). In addition, the global hypomethylation was associated with the poor disease-specific survival in TSCC patients (adjusted hazard ratio: 1.55, P = 0.043), especially for patients in older age group (> 50 years, P = 0.013), with moderate or poor cell differentiation (P = 0.044), early stage of disease (I-II, P = 0.046), small tumor size (T1-T2, P = 0.005), without lymph node involvement (P = 0.041), and ever received postoperative radiotherapy (P = 0.009).	To evaluate any geographical variations in practice and adherence to international guidelines for early delivery room management of extremely low birthweight (ELBW) infants in the North, Centre and South of Italy. A questionnaire was sent to all 107 directors of Italian level III centres between April and August 2012. There was a 92% (n = 98) response rate. A polyethylene bag/wrap was used by 54 centres (55.1%), with the highest rate in Northern Italy (77.5%) and the lowest rate in Southern (37.7%) areas. In Northern regions, one centre (2.5%) said it used oxygen concentrations >40% to initiate positive pressure ventilation in ELBW infants. These proportions were higher in the Central (14.3%) and Southern (16.2%) areas. A T-piece device for positive pressure ventilation was more frequently available in the Northern (95%) units than in those in the Central (66.7%) and Southern (69.4%) regions. A median of 13% (IQR: 5%-30%) of ELBW infants received chest compressions at birth in Italy: 5%, 18% and 22% in Northern, Central and Southern units, respectively.
Do inhaled corticosteroids influence the early inflammatory response and clinical presentation of hospitalized subjects with COPD exacerbation?	Inhaled corticosteroids are anti-inflammatory medications that can down-regulate the immunologic response in patients with COPD; however, their role at onset of COPD exacerbation is still not understood. The aim of this study was to assess the early inflammatory response and clinical presentation of patients with COPD exacerbation mediated by inhaled corticosteroids. Prospective data were collected on 123 hospitalized subjects with COPD exacerbation over a 30-month period at 2 Spanish university hospitals. Based on domiciliary use, comparative analyses were performed between subjects who did not use inhaled corticosteroids (n = 58) and subjects who did (n = 65). Measurements of serum biomarkers were recorded on admission to the hospital (day 1) and on day 3; clinical, physiological, microbiological, and severity data and mortality/readmission rates were also recorded. At days 1 and 3, both groups showed a similar inflammatory response; fluticasone produced lower levels of interleukin-8 compared with budesonide (P < .01). All clinical features considered were similar in the 2 groups; multivariate analysis predicting clinical complications on hospitalization showed air-flow obstruction severity as the only predictive factor (odds ratio 3.13, 95% CI 1.13-8.63, P = .02).	All human chromosomes are capped by tandem repeat (TTAGGG)n sequences that protect them against end-to-end fusion and are essential to chromosomal replication and integrity. Therefore, after a chromosomal breakage, the deleted chromosomes must be stabilized by retaining the telomere or acquiring a new cap, by telomere healing or telomere capture. There are few reports with molecular approaches on the mechanisms involved in stabilization of 18q terminal deletions. In this study we analyzed nine patients with 18q terminal deletion identified by G-banding and genomic array. FISH using PNA probe revealed telomeric signals in all deleted chromosomes tested. We fine-mapped breakpoints with customized arrays and sequenced six terminal deletion junctions. In all six deleted chromosomes sequenced, telomeric sequences were found directly attached to the breakpoints. Little or no microhomology was found at the breakpoints and none of the breaks sequenced were located in low copy repeat (LCR) regions, though repetitive elements were found around the breakpoints in five patients. One patient presented a more complex rearrangement with two deleted segments and an addition of 17 base pairs (bp).
Do [ Reasons that seedless fruits of Siraitia grosvenorii become small ]?	To study the reasons that the seedless fruits of Siraitia grosvenorii developed to smaller ones. The differences of fruit expanding, gene expressing and cell development were investigated between the triploid and diploid fruits from two strains F050 and F049. The results showed the expanding of triploid fruits was stopped about 20 days after artificial pollination, 10 days earlier than the diploid fruits. Meanwhile, it was also investigated that aux expressing level in the triploid fruits was greatly higher than that in diploid fruits, while its ipt, cyt-p450, spds, cycB, cycD1, cycD3, cdkA, cdkB, exp and xth expressing level were greatly lower than that in diploid fruits. The majority of sarcocarp cells of the triploid fruits kept in the stage of small ones comparing with the diploid fruits.	A safety event drew attention to unsafe and inappropriate payer formulary alerts. These alerts display formulary, coverage, and eligibility data from the pharmacy benefits manager in response to an electronic prescription. They are intended to redirect prescribers to medications that are covered by insurance; however, these alerts were found to be inaccurate and contribute to potentially harmful alerts. Our objective was to reduce inappropriate payer formulary alerts by 30% within 1 year and to change the ePrescribing certification requirements to prevent future instances of harm. Using process mapping we identified the changes that were required both locally and nationally through our electronic health record (EHR) vendor and ePrescribing transaction broker. We partnered with vendors to show the safety risk and to suggest modifications to the payer formulary alert content and ePrescribing certification criteria. On the basis of the new criteria, we modified and deactivated inappropriate alerts. Rates were followed weekly for 13 months and a control chart was used to track progress. From January 2014 to January 2015, we reviewed 59 325 payer formulary alerts from ambulatory care and 11 630 from the emergency department and inpatient wards. Both local and national modifications resulted in significant and sustained decreases in inappropriate alerts.
Are respiratory therapy organizational changes associated with increased respiratory care utilization?	The effect of the respiratory therapist (RT)/patient ratio and RT organizational factors on respiratory resource utilization is unknown. We describe the impact of a multi-component intervention that called for an increase in RT/patient ratio (1:14 to 1:10), improved RT orientation, and formation of a core staffing model on best practice, including spontaneous breathing trials (SBTs) and catheter and bronchoscopically directed lower respiratory tract cultures, or bronchoalveolar lavage (BAL), in both ventilated and non-ventilated patients in the ICU. We conducted a single center, quasi-experimental study comparing 651 patients with single and first admissions between April 19, 2005 and April 18, 2006 before the RT services reorganization with 1,073 patients with single and first admissions between September 16, 2007 and September 4, 2008. Baseline characteristics were compared, along with SBTs, BAL use, lower respiratory tract cultures, and chest physiotherapy. Patients in the 2 groups were similar in terms of age (52.9 ± 15.8 y vs 53.9 ± 16.4 y, P = .23), comorbidity as measured by Charlson score (2.8 ± 2.6 vs 2.8 ± 2.7, P = .56), and acuity of illness as measured by the Case Mix Index (3.2 ± 3.9 vs 3.3 ± 4.1, P = .47). Mechanically ventilated patients had similar prevalences of respiratory diseases (24.2% vs 25.1%, P = .61). There was an increase in SBTs (0.5% vs 73.1%, P < .001), chest physiotherapy (7.4% vs 21.6%, P < .001), BALs (24.0% vs 41.4%, P < .001), and lower respiratory tract cultures (21.5% vs 38.0%, P < .001) in mechanically ventilated patients post-intervention.	Powerful growth-inhibitory action has been shown for n-3 polyunsaturated fatty acids against colon cancer cells. We have previously described their ability to inhibit proliferation of colon epithelial cells in patients at high risk of colon cancer. In the work reported here we investigated the ability of docosahexaenoic acid (DHA) to potentiate the antineoplastic activity of 5-fluorouracil (5-FU) in p53-wildtype (LS-174 and Colo 320) and p53-mutant (HT-29 and Colo 205) human colon cancer cells. When in combination with DHA, 5-FU was used at concentrations ranging from 0.1 to 1.0 microM, much lower than those currently found in plasma patients after infusion of this drug. Similarly, the DHA concentrations (< or =10 microM) used in combination with 5-FU were lower than those widely used in vitro and known to cause peroxidative effects in vivo. Whereas the cells showed different sensitivity to the growth-inhibitory action of 5-FU, DHA reduced cell growth independently of p53 cellular status. DHA synergized with 5-FU in reducing colon cancer cell growth. The potentiating effect of DHA was attributable to the enhancement of the proapoptotic effect of 5-FU. DHA markedly increased the inhibitory effect of 5-FU on the expression of the antiapoptotic proteins BCL-2 and BCL-XL, and induced overexpression of c-MYC which has recently been shown to drive apoptosis and, when overexpressed, to sensitize cancer cells to the action of proapoptotic agents, including 5-FU.
Does diosgenin induce cell cycle arrest and apoptosis in human leukemia K562 cells with the disruption of Ca2+ homeostasis?	Diosgenin is a steroidal sapogenin with estrogenic and antitumor properties. In order to elucidate the mechanism of its antiproliferative activity, we investigated its effects on the cell cycle and apoptosis in human chronic myelogenous leukemia K562 cells. Cell viability was assessed via an MTT assay. Apoptosis was investigated in terms of nuclear morphology, DNA fragmentation, and phosphatidylserine externalization. Cell cycle analysis was performed via PI staining and flow cytometry (FCM). Western blotting and immunofluorescence methods were used to determine the levels of p53, cell cycle-related proteins and Bcl-2 family members. FCM was also used to estimate the changes in mitochondrial membrane potential (MMP), intracellular Ca2+ concentration and reactive oxygen species (ROS) generation. Cell cycle analysis showed that diosgenin caused G2/M arrest independently of p53. The levels of cyclin B1 and p21Cip1/Waf1 were decreased, whereas cdc2 levels were increased. Subsequent apoptosis was demonstrated with the dramatic activation of caspase-3. A dramatic decline in intracellular Ca2+ concentration was observed as an initiating event in the process of cell cycle arrest and apoptosis, which was followed by the hyperpolarization and depolarization of MMP. Generation of ROS was observed in the progression of apoptosis. The antiapoptotic Bcl-2 and Bcl-xL proteins were downregulated, whereas the proapoptotic Bax was upregulated.	To establish a non-invasive model for the assessment of portal venous pressure (PVP) based on the magnetic resonance (MR) parameters. In this prospective study, contrast-enhanced magnetic resonance imaging (MRI) scan was performed in 109 patients indicated for upper abdominal surgeries after their written consents were obtained, and intraoperative PVP measurements were completed in 92 patients. Altogether 17 patients were excluded for not undergoing surgery or unsuccessful catheterization. A linear model was constructed for estimating PVP levels in 56 patients and further validation was conducted in the other 36 patients. The PVP levels were significantly correlated with MR parameters, including splenic volume (SV), splenic venous diameter (SVD), liver/splenic volume ratio, portal venous diameter, hepatic diameter, portal venous cross-sectional area, ascites, varices and arterial portal shunts. A linear model was established as follows: PVP (mmHg) = 2.529 + 1.572 × SVD (mm) + 0.231 × SV/body mass index (× 10(4) cm(5) /kg) + 3.44 × aspartate aminotransferase-to-platelet ratio index. This model showed excellent accuracy in the detection of portal hypertension, with the area under the receiver operating characteristic curve (AUROC) of 0.945 (95% CI 0.867-1.000), with the sensitivity and specificity of 91.7% and 93.7%, respectively. The agreement analysis revealed that the predictive value using this formula closely reflected the patients' actual PVP level. Moreover, the validation confirmed the accuracy of this model for the assessment of portal hypertension [AUROC 0.935 (95% CI 0.856-1.000)].
Are plasma lipoprotein ( a ) levels associated with the severity of coronaryheart disease in Han Chinese people?	The aim of this study was to investigate the association of lipoprotein(a) [Lp(a)] with the severity of coronary heart disease (CHD) in Han Chinese people. Six hundred and seventy-nine patients with angiographically defined CHD were enrolled in this cross-sectional study. Fasting lipids were measured, and the severity of CHD was quantitatively assessed for each patient according to the number of stenotic coronary branches and the Gensini scoring system. The levels of Lp(a), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), and apolipoprotein (apo) B100 increased, while high-density lipoprotein cholesterol (HDL-C) and apoAI decreased significantly with the number of stenotic vessels. The levels of Lp(a) increased and HDL-C and apoAI decreased significantly with the Gensini scores. The logistic regression analyses showed that Lp(a) and HDL-C were independently associated with the number of stenotic coronary vessels after adjusting for age, weight, body mass index, sex, smoking, alcohol consumption, hypertension, diabetes, triglycerides, TC, LDL-C, VLDL-C, apoAI, and apoB100. However, only Lp(a) was independently associated with the Gensini scores after adjustment.	To determine if bilateral S3 lead placement during the stage I trial period improves the "success" rate for advancing to stage II (permanent) sacral neuromodulator placement. A retrospective chart review of 124 (20 male and 104 female) patients undergoing stage I sacral neuromodulation (InterStim, Medtronic, Minneapolis, Minnesota) implantation for the treatment of refractory voiding dysfunction was performed. Patients were divided into two cohorts based on unilateral versus bilateral stage I lead placement in the S3 foramina. Both groups were then evaluated and compared with regards to overall "success", defined as progression from stage I to stage II placement. Fifty-five (44%) patients underwent unilateral stage I lead placement and 69 (56%) received bilateral S3 leads. Successful stage I trials were reported in 32/55 (58%) and 53/69 (76%) of unilateral and bilateral cohorts, respectively (P = 0.03). Five wound infections were reported-2 (3.6%) following unilateral and 3 (4.3%) after bilateral stage I lead placement. No other complications were encountered.
Do coliform bacteria isolated from recreational lakes carry class 1 and class 2 integrons and virulence-associated genes?	To characterize the integron-harbouring Gram-negative bacteria in recreational lakes, with focus on the genetic content of integrons, antimicrobial resistance profiles and virulence-associated genes. The presence and structure of integrons in coliform bacteria isolated from the water of four recreational lakes located in Poznań, Poland, was determined by PCR method. Antimicrobial resistance testing was done by disc diffusion method. Virulence-associated genes in integron-bearing Escherichia coli isolates were detected by PCR. A total of 155 integron-bearing strains of coliform bacteria were cultured. Sequence analysis showed the presence of dfrA7, aadA1, dfrA1-aadA1, dfrA17-aadA5 and dfrA12-orfF-aadA2 gene cassette arrays in class 1 integrons and dfrA1-sat2-aadA1 in class 2 integrons. Higher frequency of integron-positive bacteria and higher antimicrobial resistance ranges were noted in colder months (January and November) compared with spring and summer months. The integron-harbouring E. coli carried up to nine virulence-associated genes, with the highest frequency of kpsMT (84.6%) and traT (783%), coding for group 2 capsule and determining human serum resistance respectively.	We investigated the effects of pitavastatin on angiogenesis and perfusion in C3H/He mice with unilateral hind limb ischemia. C3H/He mice treated with saline (n = 15) or pitavastatin (1 mg.kg(-1).d(-1), n = 15) per gavage for 1 week underwent unilateral hind limb ischemia surgery and were treated for another 5 weeks. Hind-limb blood flow was measured by Laser Doppler perfusion imager (LDPI, ischemic/nonischemic limb, %) at baseline, immediately after ischemia and weekly thereafter for 5 weeks. Endpoints included local vessel counts by immunofluorescence, phospho-Akt positive cell counts by immunoenzyme histochemical technique, vascular endothelial growth factors (VEGFs) expression in ischemic limbs by Western blot and serum nitric oxide metabolite (NOx) by chrome dioxide Griess method. Lower extremity perfusion was significantly improved in pitavastatin treated mice vs. controls as measured by LDPI% at 1 week post ischemia and thereafter (P < 0.05). Pitavastatin treatment was associated with significantly increased capillary count [(47 +/- 11) vs. (26 +/- 14)/per high-power field (x 200), P < 0.05] and greater percentage of phospho-Akt positive cells [(6 +/- 1) vs. (2 +/- 0)/per high-power field (x 200), P < 0.05] in ischemic limbs. Serum NOx [(77.3 +/- 21.8) vs. (52.1 +/- 11.2) mol/L, P < 0.05) and VEGF protein expression in ischemic limbs were also significantly increased in pitavastatin group than those in control group.
Does risk factors for severe injury following indoor and outdoor fall in geriatric patients?	This study was performed to examine the characteristics of indoor and outdoor falls in older patients and the factors related to severe injury in the emergency department (ED). In total, 26,515 patients fell indoors and 19,581 outdoors. The general and clinical characteristics were compared between the two groups and factors associated with severe injury following the falls were evaluated. Younger males fell more frequently outdoors than indoors. The common activities during outdoor falls were sports and leisure activities. Environmental hazards lead to more outdoor falls than indoor falls. Factors associated with severe injury after indoor falls were transport to the ED by public ambulance or from another medical facility rather than individual transportation, fall from stairs rather than fell over, and a head and neck injury rather than a lower extremity injury. Factors related to severe injury after outdoor falls were male sex, transport to the ED by public ambulance or from another medical facility or by another method rather than individual transportation, state employed, fall from stairs rather than fell over, head and neck or thorax or abdomen injury rather than a lower extremity injury.	A colorectal tumor is not an isolated entity growing in a restricted location of the body. The patient's gut environment constitutes the framework where the tumor evolves and this relationship promotes and includes a complex and tight correlation of the tumor with inflammation, blood vessels formation, nutrition, and gut microbiome composition. The tumor influence in the environment could both promote an anti-tumor or a pro-tumor response. A set of 98 paired adjacent mucosa and tumor tissues from colorectal cancer (CRC) patients and 50 colon mucosa from healthy donors (246 samples in total) were included in this work. RNA extracted from each sample was hybridized in Affymetrix chips Human Genome U219. Functional relationships between genes were inferred by means of systems biology using both transcriptional regulation networks (ARACNe algorithm) and protein-protein interaction networks (BIANA software). Here we report a transcriptomic analysis revealing a number of genes activated in adjacent mucosa from CRC patients, not activated in mucosa from healthy donors. A functional analysis of these genes suggested that this active reaction of the adjacent mucosa was related to the presence of the tumor. Transcriptional and protein-interaction networks were used to further elucidate this response of normal gut in front of the tumor, revealing a crosstalk between proteins secreted by the tumor and receptors activated in the adjacent colon tissue; and vice versa. Remarkably, Slit family of proteins activated ROBO receptors in tumor whereas tumor-secreted proteins transduced a cellular signal finally activating AP-1 in adjacent tissue.
Does 18F-FDG-PET/CT better localize active spinal infection than MRI for successful minimally invasive surgery?	Surgical debridement is often required to treat spinal infections. Successful surgery requires accurate localization of the active infections, however, current imaging technique still requires surgeons' experience to narrow the surgical fields to achieve less invasive procedures. To investigate the use of F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) for successful surgical planning. Nine patients with suspected spinal infection underwent magnetic resonance imaging (MRI) and FDG-PET/CT before surgery to locate active foci of infections. The spinal structures were divided into seven compartments at each intervertebral disc level for a total of 315 compartments investigated. The same classification system was used to design operating fields for histological correlation. FDG-PET/CT diagnosed fewer compartments as active infection (34 compartments, 10.8%) than MRI (62 compartments, 19.7%, P = 0.002). Surgical exploration was performed in 49 compartments, and demonstrated active infection in 25 compartments. The sensitivity / specificity of FDG-PET/CT was 100% / 79%, respectively, which was superior to those of MRI, 76% / 42%. Foci of active infection showed hypermetabolic activity with a SUVmax of 7.1 ± 2.6 (range, 3.0-12.7). Receiver operating characteristic (ROC) analysis indicated an optimal threshold for active spinal infection at a SUVmax of 4.2, corresponding to a sensitivity of 90.3% and specificity of 91.2%.	PolycombGroup (PcG) proteins maintain gene repression through histone modifications and have been implicated in stem cell regulation and cancer. EZH2 is part of Polycomb Repressive Complex 2 (PRC2) and trimethylates H3K27. This histone mark recruits the BMI1-containing PRC1 that silences the genes marked by PRC2. Based on their role in stem cells, EZH2 and BMI1 have been predicted to contribute to a poor outcome for cancer patients. We have analysed the expression of EZH2 and BMI1 in a well-characterised dataset of 295 human breast cancer samples. Interestingly, although EZH2 overexpression correlates with a poor prognosis in breast cancer, BMI1 overexpression correlates with a good outcome. Although this may reflect transformation of different cell types, we also observed a functional difference. The PcG-target genes INK4A and ARF are not expressed in tumours with high BMI1, but they are expressed in tumours with EZH2 overexpression. ARF expression results in tumour protein P53 (TP53) activation, and we found a significantly higher proportion of TP53 mutations in tumours with high EZH2. This may explain why tumours with high EZH2 respond poorly to therapy, in contrast to tumours with high BMI1.
Does neostigmine but not sugammadex impair upper airway dilator muscle activity and breathing?	Cholinesterase inhibitor-based reversal agents, given in the absence of neuromuscular block, evoke a partial upper airway obstruction by decreasing skeletal upper airway muscle function. Sugammadex reverses neuromuscular block by encapsulating rocuronium. However, its effects on upper airway integrity and breathing are unknown. Fifty-one adult male rats were anaesthetized with isoflurane, tracheostomized, and a femoral artery and vein were cannulated. First, we compared the efficacy of sugammadex 15 mg kg(-1) and neostigmine 0.06 mg kg(-1) to reverse respiratory effects of rocuronium-induced partial paralysis [train-of-four ratio (T4/T1)=0.5]. Subsequently, we compared the safety of sugammadex and neostigmine given after recovery of the T4/T1 to 1, by measuring phasic genioglossus activity and breathing. During partial paralysis (T4/T1=0.5), time to recovery of minute volume to baseline values was 10.9 (2), 75.8 (18), and 153 (54) s with sugammadex, neostigmine, and placebo, respectively (sugammadex was significantly faster than neostigmine and placebo, P<0.05). Recovery of T4/T1 was also faster for sugammadex than neostigmine and placebo. Neostigmine administration after complete recovery of T4/T1 decreased upper airway dilator muscle activity to 64 (30)% of baseline and decreased tidal volume (P<0.05 for both variables), whereas sugammadex had no effect on either variable.	To identify molecular features associated with clinico-pathological parameters in renal cell cancer. Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging was employed for a kidney cancer tissue microarray containing tissue samples from 789 patients for which clinical follow-up data were available. A comparison of mass spectrometric signals with clinico-pathological features revealed significant differences between papillary and clear cell renal cell cancer. Within the subgroup of clear cell RCC, statistical associations with tumor stage (seven signals, p<0.01 each), Fuhrman grade (seven signals, p<0.0001 each), and presence of lymph node metastases (10 signals, p<0.01 each) were found. In addition, the presence of one signal was significantly linked to shortened patient survival (p=0.0198).
Does glycine attenuate endotoxin-induced liver injury by downregulating TLR4 signaling in Kupffer cells?	Several experimental studies have observed better outcomes after glycine treatment in patients with endotoxin-induced liver injuries, but its molecular mechanism is not yet fully understood. The purpose of this study was to evaluate the hypothesis that glycine attenuates endotoxin-induced liver injury by affecting endotoxin signal transduction in liver macrophages. An animal model of endotoxin-induced liver injury was established by intraperitoneally injecting mice with 10 mg/kg body weight endotoxin fed a pretreatment diet with or without 5% (w/w) glycine. Blood and liver samples were obtained for analysis of liver morphology and to determine concentrations of alanine aminotransferase, endotoxin receptor Toll-like receptor 4 (TLR4), tumor necrosis factor-alpha (TNF-alpha), and interleukin (IL)-10 at various time points after injection. To investigate the effect of glycine on liver macrophages, Kupffer cells (KCs) were isolated and challenged by LPS (100 ng/mL), with or without glycine (4 mmol/l) pretreatment, and the expressions of TLR4, IL-10, and TNF-alpha were assayed at mRNA and protein levels. DNA-binding activity of nuclear factor-kappa B (NF-kappaB) was also analyzed using enzyme-linked immunosorbent assay. Dietary glycine significantly improved the survival rate of endotoxemic mice (P < .05), whereas serum alanine aminotransferase and TNF-alpha levels were significantly decreased at different time points (P < .05); IL-10 levels were increased (P < .05). Concurrently, LPS-induced hepatic tissue injury was attenuated as indicated by morphologic analysis; secretion of IL-10 in liver tissue (P < .05) was enhanced; and expression of TLR4 and TNF-alpha in liver tissue was downregulated (P < .05). Consistent with these in vivo experiments, enhanced secretion of IL-10 and inhibited expression of TLR4 and TNF-alpha caused by glycine pretreatment were also observed in LPS-stimulated KCs. NF-kappaB DNA-binding activity was also significantly inhibited by glycine (P < .05, respectively).	Knowledge concerning hormone replacement therapy (HRT) is rapidly changing. We sought to understand the factors that influence how residents assimilate this knowledge. We conducted an anonymous survey of residents in an internal medicine residency. Questions included personal demographic information and aspects of training (didactic and experiential) regarding and knowledge about HRT. Data were analyzed using univariable and multivariable linear regression. Sixty-nine of 92 residents (75%) completed the survey. The gender and race of respondents did not differ significantly from the overall group. Knowledge scores were higher among residents in nontraditional (Women's Health, Primary Care, and Internal Medicine-Pediatrics) training tracks (p = .04) and among residents with patient population of < or = 30% postmenopausal women (p = .049). Demographic characteristics and didactic training about HRT did not influence knowledge.
Does leucocyte count indicate carotid plaque instability in stroke patients?	Increasing evidence points to the inflammatory character of atherosclerosis and several parameters of inflammation have been proposed as cerebrovascular risk markers. The objective of the research was to examine the connection of serum inflammatory parameters and ultrasound (US) characteristics of the structure and size of carotid plaque. We assumed that the number of leukocytes (Le) was an indicator of carotid plaque instability and an increased risk of stroke. Serum inflammatory parameters: erythrocyte sedimentation rate in the first (ESR I) and second hour (ESR II), the number of Le, high sensitivity C-reactive protein (hsCRP) and fibrinogen were measured by standard methods. All the subjects (n = 75) were divided into 3 groups (symptomatic, asymptomatic and control). US evaluation of extracranial carotid arteries was performed in a duplex system. Plaques were classified into categories according to stenosis percentage (≥ 50%, < 50%) and pursuant to echomorphological characteristics (Gray-Weale classification). In the subjects with stroke an ischemic lesion was confirmed by computed tomography. The average values of biochemical parameters in the symptomatic group were: ESR I 29.57 ± 29.87 cm, ESR II 51.60 ± 36.87 cm, the number of Le 10.10 ± 3.20 x 10⁹ U/L, hsCRP 8.15 ± 5.50 mg/L and fibrinogen 4.03 ± 0.70 g/L. The average values of all testing biochemical parameters in symptomatic patients were significantly higher than in the asymptomatic ones and the control group: for ESR I (p < 0.05) and ESR II (p < 0.05); for the number of Le (p < 0.001); for hsCRP (p < 0.001) and fibrinogen (p < 0.001). Category I of echomorphological characteristics in the symptomatic group was present in 66.7% of the cases and it was significantly higher than in the asymptomatic (40.0%; p < 0.05) and the control group (20.0%; p < 0.01). Univariate logistic regression analysis confirmed that all testing biochemical parameters are indicators of stroke risk. Multivariate logistic regression analysis confirmed a statistically significant correlation of the number of Le and stroke risk, while the increase in the value by a unit of measurement was associated with the growth of risk by 3.22 times (from 1.67 to 6.22).	The Boston HAPPENS (HIV Adolescent Provider and Peer Education Network for Services) program is a collaborative network of care made up of 8 organizations that serve youth and provide coordinated care for human immunodeficiency virus (HIV)-positive, homeless, and at-risk youth aged 12 to 24 years. Learning youth perceptions about the program is essential to determine if the program is meeting their needs. In this qualitative evaluation, 18 youth served by the network met in 4 focus groups to provide their view of the program. Services within 5 categories were assessed: (a) medical care, (b) mental health and substance abuse care, (c) HIV prevention and care, (d) case management, and (e) allocation of finances. Boston HAPPENS has achieved name recognition and provides many needed services for youth from a wide variety of backgrounds. The youth were comfortable receiving care and were appreciative of the comprehensive services available. They provided suggestions for how mental health services could be offered as one-on-one counseling as part of "wellness care." Young participants also requested more recreational and support opportunities for young people living with HIV.
Does patient-controlled epidural analgesia in labor always improve maternal satisfaction?	We investigated whether patient-controlled epidural analgesia in labor with bupivacaine and fentanyl provides more satisfaction to mothers than intermittent bolus epidural analgesia or patient-controlled epidural analgesia with plain bupivacaine. Ninety mothers with term, uncomplicated pregnancies were randomized to receive intermittent bolus epidural analgesia (bupivacaine + fentanyl), patient-controlled epidural analgesia (bupivacaine + fentanyl), or patient-controlled epidural analgesia (bupivacaine). Pain during labor was evaluated with a visual analog scale. Obstetric and neonatal outcomes were recorded. After delivery, the mothers were given a questionnaire covering the following themes: experience of labor pain, feeling of control, fears and expectations associated with pregnancy/with delivery/with becoming a mother, as well as pain, physical condition and emotions after delivery. To elaborate on these answers, 30 mothers were further randomized to a semistructured interview, in which the same topics were discussed. The main outcome measure was maternal satisfaction. The intermittent bolus epidural analgesia group felt they could influence labor most (p = 0.03), and in the interview they expressed most satisfaction. In this group, the total drug utilization was smallest (bupivacaine: p <0.0001 comparing all groups, fentanyl: p = 0.03 comparing the two fentanyl-receiving groups). No differences in pain occurred. Vomiting (p = 0.04) and pruritus (p <0.0001) were more common or more severe in the groups receiving fentanyl.	Mesenchymal stromal cells (MSCs) have powerful immunosuppressive activity. This function of MSCs is attributed to plethora of the expressed immunosuppressive factors, such as galectin-1 (Gal-1), a pleiotropic lectin with robust anti-inflammatory effect. Nevertheless, whether Gal-1 renders or contributes to the immunosuppressive effect of MSCs has not been clearly established. Therefore, this question was the focus of a complex study. MSCs were isolated from bone marrows of wild-type and Gal-1 knockout mice and their in vitro anti-proliferative and apoptosis-inducing effects on activated T cells were examined. The in vivo immunosuppressive activity was tested in murine models of type I diabetes and delayed-type hypersensitivity. Both Gal-1-expressing and -deficient MSCs inhibited T-cell proliferation. Inhibition of T-cell proliferation by MSCs was mediated by nitric oxide but not PD-L1 or Gal-1. In contrast, MSC-derived Gal-1 triggered apoptosis in activated T cells that were directly coupled to MSCs, representing a low proportion of the T-cell population. Furthermore, absence of Gal-1 in MSCs did not affect their in vivo immunosuppressive effect.
Is predictive value of the preablation serum thyroglobulin level after thyroidectomy combined with postablation 131I whole body scintigraphy for successful ablation in patients with differentiated thyroid carcinoma?	To investigate the clinical importance of the combined use of serum thyroglobulin (Tg) levels measured just before ablation (ablation-Tg) and postablation 131I whole body scintigraphy (WBS) patterns for predicting ablation success in patients with differentiated thyroid carcinoma who received total thyroidectomy and 131I ablation therapy. We retrospectively studied the early clinical outcomes for 81 differentiated thyroid carcinoma patients treated with total thyroidectomy and high-dose 131I ablation therapy between June 2001 and July 2004. Ablation success was achieved in 42 (97.7%) of the 43 patients with uptake in the thyroid bed only and ablation-Tg levels less than 10 ng/mL, whereas successful ablation was achieved in 9 (75.0%) of the 12 patients with uptake in the thyroid bed only and ablation-Tg levels equal to or greater than 10 ng/mL (P = 0.029). Among 15 patients with uptake including a lymph node and ablation-Tg levels less than 10 ng/mL, 14 patients (93.3%) showed ablation success, whereas successful ablation was achieved in only 2 (18.2%) of the 11 patients with uptake including a lymph node and ablation-Tg levels equal to or greater than 10 ng/mL (P < 0.001).	Parkinson's disease (PD) is the second most common neurodegenerative movement disorder, caused by preferential dopaminergic neuronal cell death in the substantia nigra, a process also influenced by oxidative stress. L-3,4-dihydroxyphenylalanine (L-DOPA) represents the main treatment route for motor symptoms associated with PD however, its exact mode of action remains unclear. A spectrum of conflicting data suggests that L-DOPA may damage dopaminergic neurons due to oxidative stress whilst other data suggest that L-DOPA itself may induce low levels of oxidative stress, which in turn stimulates endogenous antioxidant mechanisms and neuroprotection. In this study we performed a two-dimensional gel electrophoresis (2DE)-based proteomic study to gain further insight into the mechanism by which L-DOPA can influence the toxic effects of H2O2 in neuronal cells. We observed that oxidative stress affects metabolic pathways as well as cytoskeletal integrity and that neuronal cells respond to oxidative conditions by enhancing numerous survival pathways. Our study underlines the complex nature of L-DOPA in PD and sheds light on the interplay between oxidative stress and L-DOPA.
Does analysis of the priming activity of lipids generated during routine storage of platelet concentrate?	Compounds generated during the routine storage of platelet concentrates may have deleterious effects on the transfusion recipient. Daily plasma samples from platelet concentrates, both apheresis platelets and those separated from whole blood, were obtained serially during routine storage. These plasma samples were assayed for their ability to prime the NADPH oxidase in isolated human neutrophils. Quantitative and qualitative analysis of the priming agents was completed by lipid extraction, high-pressure liquid chromatography separation, and gas chromatography/mass spectroscopy. Compounds were generated in both apheresis and whole-blood platelets that significantly primed the NADPH oxidase after 24 and 48 hours of storage, respectively. The priming activity was maximal by component outdate: 2.6-fold that of the buffer-treated control neutrophils (apheresis) and 3.9-fold that of the buffer-treated control neutrophils (whole blood). These agents were generated by cellular constituents, as stored plasma did not demonstrate such priming activity. Inhibition of this priming activity by WEB 2170, a specific platelet-activating factor receptor antagonist, suggested that the observed priming involved the platelet-activating factor receptor. A portion of the priming activity from platelet concentrates was organically extractable: 69 percent of that from apheresis platelets and 46 percent of that from whole-blood platelets. Further purification of the lipid's priming activity by normal-phase high-pressure liquid chromatography demonstrated a single peak of priming activity at the retention time of lysophosphatidylcholines. Because 46 percent of the priming activity from whole-blood platelets was chloroform insoluble and because it has been reported that interleukin 8 is generated during routine storage of whole-blood platelets, the effects of interleukin 8 on the NADPH oxidase were examined. Recombinant monocyte interleukin 8 rapidly primed the oxidase but was not inhibited by WEB 2170.	The caudal-type homeodomain transcriptional factor CDX2, a member of the caudal-related homeobox gene family, plays a crucial role in the regulation of cell proliferation and differentiation in the gut. Recent studies have reported that expression of CDX2 was an independent marker of outcome in patients with resected adenocarcinoma of ampulla of Vater, gastric cancer, and colon cancer. The clinicopathological significance of CDX2 expression has hitherto remained unclear in biliary tract carcinoma (BTC). The aim of this study was to determine whether CDX2 expression in BTC indicates clinical outcome. The expression of CDX2 was investigated immunohistochemically in surgically resected specimens from 164 patients with BTC, including 74 intrahepatic cholangiocarcinomas, 49 extrahepatic cholangiocarcinomas, and 41 gallbladder carcinomas. The correlation between expression of CDX2 and clinicopathological factors, including overall survival, tumor location, tumor stage, and degree of tumor differentiation, was examined in patients with BTC. In total, 27 of the 164 (16.46%) patients with BTC expressed CDX2. The frequency of CDX2 expression was much higher in the extrahepatic cholangiocarcinomas (22.45%) and gallbladder carcinomas (29.27%) than in the intrahepatic cholangiocarcinomas (5.41%), the difference being statistically significant (P = 0.002). Factors influencing survival on univariate analysis were tumor stage (P < 0.00001), degree of tumor differentiation (P = 0.0002), and CDX2 expression (P = 0.01). On multivariate analysis using the Cox proportional hazard model, CDX2 expression and tumor stage were independent prognostic factors in patients with BTC.
Is area under the serum creatinine time-curve a strong predictor of chronic renal allograft rejection?	A number of risk factors for chronic renal allograft rejection have been identified; in particular the number and severity of acute rejections, hypertension, hyperlipidemia, and insufficient immunosuppression. In a retrospective case control study, all histologically confirmed cases of chronic rejection (n=45) that occurred between 1985 and 1993 among patients transplanted at Huddinge Hospital were compared with twice as many controls. Determinants such as donor age and sex, HLA-mismatch, cold ischemia time, recipient age and sex, body mass index, cause of renal disease, time undergoing dialysis, condition of blood vessels at surgery, time of onset, number of acute rejection episodes during the first 3 months, area under the serum creatinine versus time curve (AUC(Creatinine)), blood pressure, blood lipids, and cyclosporine concentrations at various times after the transplantation were also compared. Additional data were obtained from a questionnaire, concerning 79% of the cases and controls. Cases and controls were similar with regard to most determinants, that is, blood pressure, blood lipids, and average cyclosporine concentrations. The main outstanding risk factor for chronic rejection was the time-averaged creatinine (AUC(Creatinine)) value between day 22 and 3 months after transplantation. The adjusted odds ratio for chronic rejection increased stepwise from 1.1 to 9.2, when AUC(Creatinine) increased from < 150 to >300 micromol/l. The number of acute rejection episodes and number of HLA-mismatches also had a significant effect on the risk of chronic rejection.	Neuroblastoma, a frequently occurring solid tumour in children, remains a therapeutic challenge as existing imaging tools are inadequate for proper and accurate diagnosis, resulting in treatment failures. Nanoparticles have recently been introduced to the field of cancer research and promise remarkable improvements in diagnostics, targeting and drug delivery. Among these nanoparticles, quantum dots (QDs) are highly appealing due to their manipulatable surfaces, yielding multifunctional QDs applicable in different biological models. The biocompatibility of these QDs, however, remains questionable. We show here that QD surface modifications with N-acetylcysteine (NAC) alter QD physical and biological properties. In human neuroblastoma (SH-SY5Y) cells, NAC modified QDs were internalized to a lesser extent and were less cytotoxic than unmodified QDs. Cytotoxicity was correlated with Fas upregulation on the surface of treated cells. Alongside the increased expression of Fas, QD treated cells had increased membrane lipid peroxidation, as measured by the fluorescent BODIPY-C11 dye. Moreover, peroxidized lipids were detected at the mitochondrial level, contributing to the impairment of mitochondrial functions as shown by the MTT reduction assay and imaged with confocal microscopy using the fluorescent JC-1 dye.
Do gold nanoparticles induce cytotoxicity in the alveolar type-II cell lines A549 and NCIH441?	During the last years engineered nanoparticles (NPs) have been extensively used in different technologies and consequently many questions have arisen about the risk and the impact on human health following exposure to nanoparticles. Nevertheless, at present knowledge about the cytotoxicity induced by NPs is still largely incomplete. In this context, we have investigated the cytotoxicity induced by gold nanoparticles (AuNPs), which differed in size and purification grade (presence or absence of sodium citrate residues on the particle surface) in vitro, in the human alveolar type-II (ATII)-like cell lines A549 and NCIH441. We found that the presence of sodium citrate residues on AuNPs impaired the viability of the ATII-like cell lines A549 and NCIH441. Interestingly, the presence of an excess of sodium citrate on the surface of NPs not only reduced the in vitro viability of the cell lines A549 and NCIH441, as shown by MTT assay, but also affected cellular proliferation and increased the release of lactate dehydrogenase (LDH), as demonstrated by Ki-67 and LDH-release assays respectively. Furthermore, we investigated the internalization of AuNPs by transmission electron microscopy (TEM) and we observed that particles were internalized by active endocytosis in the cell lines A549 and NCIH441 within 3 hr. In addition, gold particles accumulated in membrane-bound vesicles and were not found freely dispersed in the cytoplasm.	Non-dipper pattern, characterized by diminished nocturnal decline in blood pressure (BP), is associated with an increase in cardiovascular events. Carotid-femoral pulse wave velocity (CF-PWV) has been accepted as the gold standard measurement of arterial stiffness. CF-PWV is a well-recognized predictor of an adverse cardiovascular outcome with higher predictive value than classical cardiovascular risk factors. In this study, we investigated the association between PWV as the surrogate of arterial stiffness and non-dipper pattern in untreated hypertensive patients. The present study was cross-sectional and observational. Hypertensive patients were diagnosed according to ambulatory BP measurements (mean BP ≥ 130/80 mmHg). Eighty-four hypertensive patients, consulted for initial evaluation of hypertension, were enrolled. CF-PWV as the indicator of arterial stiffness was measured by a validated tonometry system (SphygmoCor). Patients with the history of any cardiovascular disease were excluded from the study. Fifty-six patients had non-dipper pattern and 28 patients had dipper pattern in the study. Baseline characteristics were not significantly different between the two groups, except the CF-PWV (non-dipper vs dipper; 8.91 ± 2.53 vs 7.66 ± 1.08 m/s, p = 0.002), female gender (55% vs 32%, p = 0.045) and nocturnal BP measurements (for mean BP; 106 ± 11 vs 92 ± 8 mmHg, p < 0.001). Multiple logistic regression analysis including age, gender, BP and PWV measurements, revealed female gender (odds ratio, OR = 5.112, 95% confidence interval, CI 1.282-20.4, p = 0.021), nocturnal mean BP (OR = 1.243, 95% CI 1.107-1.396, p < 0.001) and CF-PWV (OR = 1.992, 95% CI 1.240-3.198, p = 0.004) as the independent predictors of non-dipper hypertensive pattern.
Does hypoxia regulate human lung fibroblast proliferation via p53-dependent and -independent pathways?	Hypoxia induces the proliferation of lung fibroblasts in vivo and in vitro. However, the subcellular interactions between hypoxia and expression of tumor suppressor p53 and cyclin-dependent kinase inhibitors p21 and p27 remain unclear. Normal human lung fibroblasts (NHLF) were cultured in a hypoxic chamber or exposed to desferroxamine (DFX). DNA synthesis was measured using bromodeoxyuridine incorporation, and expression of p53, p21 and p27 was measured using real-time RT-PCR and Western blot analysis. DNA synthesis was increased by moderate hypoxia (2% oxygen) but was decreased by severe hypoxia (0.1% oxygen) and DFX. Moderate hypoxia decreased p21 synthesis without affecting p53 synthesis, whereas severe hypoxia and DFX increased synthesis of both p21 and p53. p27 protein expression was decreased by severe hypoxia and DFX. Gene silencing of p21 and p27 promoted DNA synthesis at ambient oxygen concentrations. p21 and p53 gene silencing lessened the decrease in DNA synthesis due to severe hypoxia or DFX exposure. p21 gene silencing prevented increased DNA synthesis in moderate hypoxia. p27 protein expression was significantly increased by p53 gene silencing, and was decreased by wild-type p53 gene transfection.	To investigate the relationship between mean platelet volume (MPV) and glycometabolic indices, to compare MPV according to HbA1c levels, and to analyse the difference in MPV between patients with and without microvascular complications. This retrospective study was conducted on 60 Type 2 diabetic patients and 50 age- and sex-matched non-diabetic controls. We obtained demographic, clinical and laboratory data including MPV, platelet count, fasting and postprandial blood glucose (FBG and PBG), haemoglobin A1c (HbA1c), lipid profile, creatinine, systolic and diastolic blood pressure (BP) in patient and control groups, and diabetic microvascular complications including nephropathy, neuropathy, and retinopathy in the patient group. All analyses were performed using SPSS version 15.0 for Windows. Mean platelet volume in the diabetic group was higher than in the control group (p = 0.001). Mean platelet volume was positively correlated with FBG and HbA1c levels (p = 0.03 and p < 0.001, respectively). It was also negatively related to platelet count (p < 0.001). Mean platelet volume in patients with HbA1c > 7% was significantly higher than those with HbA1c ≤ 7% (p < 0.001). Mean platelet volume was significantly increased in patients with retinopathy compared to those without retinopathy (p = 0.04).
Is severe reflux disease associated with an enlarged unbuffered proximal gastric acid pocket?	An unbuffered pocket of highly acidic juice is observed at the gastric cardia after a meal in healthy subjects. To compare the postprandial acid pocket in healthy subjects and patients with severe reflux disease and define its position relative to anatomical and manometric landmarks. 12 healthy subjects and 16 patients with severe reflux disease were studied. While fasted, a station pull-through was performed using a combined dual pH and manometry catheter. Position was confirmed by radiological visualisation of endoscopically placed radio-opaque clips. The pull-through study was repeated 15 min after a standardised fatty meal. Barium meal examination was performed before and following the meal. A region of unbuffered acid (pH <or=2) immediately distal to the proximal gastric folds was more frequent in reflux patients (23/32 studies) than in healthy subjects (11/24) (p<0.05). This unbuffered acid pocket was longer in the reflux patients than in the healthy subjects (median length 3 cm (range 1-15) vs 2 cm (range 1-5); p<0.05). The acid pocket extended proximally as far as the proximal gastric folds in the patients but stopped a median of 1.1 cm distal in healthy subjects (p = 0.005). In healthy subjects the acid pocket occupied the distal portion of the sphincter which opened postprandially, whereas in reflux patients it corresponded to the proximal displacement of the gastric folds--that is, hiatus hernia.	Autologous hematopoietic stem cell transplantation (auto-HSCT) patients experience long-term immunosuppression, which increases susceptibility to infection and relapse rates due to minimal residual disease (MRD). Sex steroid (SS) ablation is known to reverse age-related thymic atrophy and decline in B-cell production This study used a congenic HSCT mouse model to analyze the effects of SS ablation (through surgical castration) on immune reconstitution and growth factor production following auto-HSCT. Bone marrow (BM) and thymic stromal cell (TSCs) populations were analyzed using RT-PCR and were tested for the production of growth factors previously implicated in immune reconstitution or age-relate immune degeneration Castration increased bone marrow (BM), thymic, and splenic cellularity following auto-HSCT. HSC number and common lymphoid precursor (CLP) frequency and number were increased in castrated mice. B cell precursor numbers were also significantly increased in the BM of these mice. Triple negative, double positive and single positive thymocytes were increased following HSCT and castration, as were thymic dendritic cells and natural killer T (NKT) cells. This enhanced lymphoid reconstitution of the primary immune organs leads to a significant increase in splenic T and B cells 42 days after HSCT. The molecular mechanisms behind the enhanced reconstitution were also studied. TGF-beta1 was decreased in castrated mice compared to sham-castrated controls in TSCs and BM cells. TSC production of IL-6 was also decreased in castrated mice
Is albumin-adjusted calcium suitable for diagnosis of hyper- and hypocalcemia in the critically ill?	To evaluate whether calcium adjusted for albumin can be used to monitor calcium homeostasis in critically ill patients. Prospective single-single center observational study. Clinical laboratory and critical care unit of a regional teaching hospital. Fifty-three paired samples were from 36 patients requiring intensive care treatment. None. Total calcium, albumin-adjusted calcium, and ionized calcium were measured in critically ill patients during an 8-wk period. Calcium was adjusted for albumin using the formula that is most frequently used in The Netherlands. Using ionized calcium as the gold standard, albumin-adjusted calcium overestimated hypercalcemia and totally missed hypocalcemia. The same seemed to be true for other formulas used for albumin or protein adjustment of calcium concentrations.	Autoimmune hepatitis (AIH) is an uncommon autoimmune liver disease of unknown etiology. We used a genome-wide approach to identify genetic variants that predispose individuals to AIH. We performed a genome-wide association study of 649 adults in The Netherlands with AIH type 1 and 13,436 controls. Initial associations were further analyzed in an independent replication panel comprising 451 patients with AIH type 1 in Germany and 4103 controls. We also performed an association analysis in the discovery cohort using imputed genotypes of the major histocompatibility complex region. We associated AIH with a variant in the major histocompatibility complex region at rs2187668 (P = 1.5 × 10(-78)). Analysis of this variant in the discovery cohort identified HLA-DRB10301 (P = 5.3 × 10(-49)) as a primary susceptibility genotype and HLA-DRB10401 (P = 2.8 × 10(-18)) as a secondary susceptibility genotype. We also associated AIH with variants of SH2B3 (rs3184504, 12q24; P = 7.7 × 10(-8)) and CARD10 (rs6000782, 22q13.1; P = 3.0 × 10(-6)). In addition, strong inflation of association signal was found with single-nucleotide polymorphisms associated with other immune-mediated diseases, including primary sclerosing cholangitis and primary biliary cirrhosis, but not with single-nucleotide polymorphisms associated with other genetic traits.
Does intestinal lipid absorption increase cold ischemia of the small bowel in rats?	The short cold ischemic tolerance of the gut is a major problem in small bowel transplantation. We have shown that intestinal lipid administration is beneficial during systemic inflammation like sepsis. Rats were intestinally infused with either water or 1% olive oil for 12 hours. The small bowel was removed and stored in HTK solution on ice. At t = 0, t = 60, t = 120, t = 180, t = 240, t = 300, t = 360, t = 420, and t = 480 minutes, a tissue sample of the gut was fixed, stained, and analyzed by three independent observers. Damage score was calculated (0 = no damage, 1 = minor damage, 2 = major damage, 3 = loss of structure) for integrity of the mucosa, integrity of the basal membrane of the mucosa, and integrity of villy. The damage score was allocated when all three observers agreed on the same or a higher damage score. In all control animals minor damage for the integrity of the basal membrane occurred within 60 minutes, but in only 50% of the lipid-treated rats. In all control rats, major damage for both integrity of mucosa and villi occurred within 300 minutes or less, but only in 50% of the lipid-treated rats. In all control rats, the structure of the villi was completely lost within 480 minutes or less, whereas only 50% of the lipid treated animals reached maximal damage scores for either mucosa or villi.	To obtain a global perspective on the distribution and evolution of CYP1B1 mutations in primary congenital glaucoma (PCG) worldwide. Five intragenic single-nucleotide polymorphisms in CYP1B1-R48G, A119S, V432L, D449D, and N453S-were used to generate haplotype data from 138 Indian patients with PCG and 132 ethnically matched normal controls, which were then analyzed in conjunction with data from other populations. Maximum-likelihood estimates of haplotype frequencies were estimated from the genotype data. Subsets of patients and normal control subjects were also genotyped with respect to eight short tandem repeat (STR) markers around the CYP1B1 locus (D2S305, D2S165, D2S367, D2S2259, D2S391, D2S3337, D2S23678, and D2S286), to gain evolutionary insights. Common mutations in CYP1B1 that are causal of PCG occurred on a uniform haplotype background among Indian patients, which is completely distinct from the modal haplotype background found among unaffected control subjects. Comparison of these data with data from other global regions reveals strong clustering of CYP1B1 mutations by geographic and haplotype backgrounds. The two distinct modal haplotypes found among Indian patients with PCG and control subjects are both ancient with ages of similar magnitudes, as indicated by large variances in the number of repeats at eight STR loci. Together with data from chimpanzee and normal control subjects from India and other global regions, it was possible to make a parsimonious reconstruction of the evolution of these haplotypes.
Are cardiac histones substrates of histone deacetylase activity in hemorrhagic shock and resuscitation?	DNA transcription is regulated, in part, by acetylation of nuclear histones that are controlled by 2 groups of enzymes: histone deacetylases (HDAC) and histone acetyl transferases (HAT). Whether an imbalance in HDAC/HAT system plays a role in hemorrhage/resuscitation is unknown. The goals of this study were to determine whether hemorrhage results in deacetylation of cardiac histones and whether this can be corrected through the application of different resuscitation strategies or specific HDAC inhibitors. In the first experiment, rats (n = 6 per group) were subjected to volume-controlled hemorrhage and resuscitated with racemic lactated Ringer's solution, L-lactated Ringer's solution, 7.5% hypertonic saline solution, ketone Ringer's solution, and pyruvate Ringer's solution. Control groups included no hemorrhage (sham) and hemorrhage with no resuscitation. In the second experiment (n = 5 per group), 3 HDAC inhibitors (valproic acid, trichostatin A, and suberoylanilide hydroxamic acid) were added to saline solution resuscitation. Heart tissue was collected at the end of resuscitation. Isolated subcellular protein fractions were used in Western blotting to analyze the patterns of total protein acetylation and histone acetylation specifically. HDAC and HAT activity was measured in tissue extracts. Hemorrhage led to partial histone deacetylation. Resuscitation resulted in protein hyperacetylation in nuclear fractions only. A detailed analysis of histones (on 10 acetylation sites) revealed that ketone Ringer's solution hyperacetylated histones H2B, H3, and H4. The addition of suberoylanilide hydroxamic acid hyperacetylated histones more effectively than other resuscitation strategies, presumably by direct inhibition of HDAC activity.	To evaluate the thickness of cartilage at the posterior aspect of the medial and lateral condyle in Osteoarthritis (OA) knees compared to non-OA knees using computed tomography arthrography (CTA). 535 consecutive knee CTAs (mean patient age = 48.7 ± 16.0; 286 males), were retrospectively analyzed. Knees were radiographically classified into OA or non-OA knees according to a modified Kellgren/Lawrence (K/L) grading scheme. Cartilage thickness at the posterior aspect of the medial and lateral femoral condyles was measured on sagittal reformations, and compared between matched OA and non-OA knees in the whole sample population and in subgroups defined by gender and age. The cartilage of the posterior aspect of medial condyle was statistically significantly thicker in OA knees (2.43 mm (95% confidence interval (CI) = 2.36, 2.51)) compared to non-OA knees (2.13 mm (95%CI = 2.02, 2.17)) in the entire sample population (P < 0.001), as well as for all subgroups of patients over 40 years old (all P ≤ 0.01), except for females above 60 years old (P = 0.07). Increase in cartilage thickness at the posterior aspect of the medial condyle was associated with increasing K/L grade in the entire sample population, as well as for males and females separately (regression coefficient = 0.10-0.12, all P < 0.001). For the lateral condyle, there was no statistically significant association between cartilage thickness and OA (either presence of OA or K/L grade).
Is smoking associated with more abdominal fat in morbidly obese patients?	While the association between cigarette smoking and abdominal fat has been well studied in normal and overweight patients, data regarding the influence of tobacco use in patients with morbid obesity remain scarce. The aim of this study is to evaluate body fat distribution in morbidly obese smokers. We employed a cross-sectional study and grouped severely obese patients (body mass index [BMI] >40 kg/m2 or >35 kg/m2 with comorbidities) according to their smoking habits (smokers or non-smokers). We next compared the anthropometrical measurements and body composition data (measured by electric bioimpedance) of both groups. We analyzed the effect of smoking on body composition variables using univariate and multiple linear regression (MLR); differences are presented as regression coefficients (b) and their respective 95% confidence intervals. We included 536 morbidly obese individuals, 453 (84.5%) non-smokers and 83 (15.5%) smokers. Male smokers had a higher BMI (b=3.28 kg/m2, p=0.036), larger waist circumference (b=6.07 cm, p=0.041) and higher percentage of body fat (b=2.33%, p=0.050) than non-smokers. These differences remained significant even after controlling for confounding factors. For females, the only significant finding in MLR was a greater muscle mass among smokers (b=1.34kg, p=0.028). No associations were found between tobacco load measured in pack-years and anthropometric measures or body composition.	Heat shock protein-27 (HSP-27) belongs to the group of small heat shock proteins that become induced in response to various pathologic conditions. HSP-27 has been shown to protect cells and subcellular structures, particularly mitochondria, and serves as a carrier for estradiol. It is a reliable marker for tissues affected by oxidative stress. Oxidative stress and related cellular defence mechanisms are currently thought to play a major role during experimentally induced epileptic neuropathology. We addressed the question whether HSP-27 becomes induced in the neocortex resected from patients with pharmacoresistant epilepsy. Human epileptic temporal neocortex was obtained during neurosurgery, and control tissue was obtained at autopsy from subjects without known neurologic diseases. The tissues were either frozen for Western blot analysis or fixed in Zamboni's fixative for the topographic detection of HSP-27 at the cellular level by means of immunohistochemistry. HSP-27 was highly expressed in all epilepsy specimens and in the cortex of a patient who died in the final stage of multiple sclerosis (positive control), whereas only low amounts of HSP-27 were detectable in control brains. In epilepsy patients, HSP-27 was present in astrocytes and in the walls of blood vessels. The intracortical distribution patterns varied strongly among the epilepsy specimens.
Does thyroid function influence serum apolipoprotein B-48 levels in patients with thyroid disease?	Apolipoprotein B-48 (apoB-48) is a major apolipoprotein of intestine-derived chylomicrons (CM) and CM remnants (CMR). Clinically overt hypothyroidism (OH) has been associated with premature and accelerated coronary atherosclerosis. To clarify the clinical significance of apoB-48 measurement in patients with thyroid disease, we investigated the correlations between the serum apoB-48 level and thyroid hormones. From outpatients of Osaka University Hospital, patients with OH, subjects with subclinical hypothyroidism (SH) and subjects with normal thyroid function were collected and analyzed by measuring serum TSH, FT4 and FT3 levels. Serum apoB-48 levels were measured by a chemiluminescence enzyme immunoassay and the correlations with thyroid hormone levels or lipid profiles were assessed. These levels were compared among subjects with OH, SH and healthy controls. Serum apoB-48 level was correlated with TSH, total cholesterol (TC) and triglycerides (TG), but negatively with FT4 and FT3 level. LDL-C and HDL-C levels were not correlated with serum apoB-48 levels. Serum apoB-48 in patients with OH (7.4 ± 5.9 µg/mL) was significantly higher than in those with hyperthyroidism (5.1 ± 3.5 µg/mL; p<0.01) and normal subjects (4.7 ± 3.7 µg/mL; p<0.01), but decreased after levo-thyroxine replacement. ApoB-48, TG and TSH were significantly higher in SH subjects than normal subjects, suggesting that serum apoB-48 level depends on the thyroid function status, similar to TC, LDL-C and TG.	To evaluate pain behavior and structural damage in mice subjected to either meniscal transection or removal. Mice (10/group) were subjected to transection of the medial collateral and anterior cruciate ligaments (ACLT/MCLT) followed by either transection (meniscotomy) or removal (meniscectomy) of the medial meniscus. A control group was subjected only to transection of the ligaments. Pain was assessed using the electronic pressure-meter paw test. Cell influx, measured in joint exudates, and joint histopathology were assessed after 49 days. Four other groups subjected to meniscotomy received indomethacin, the inducible nitric oxide synthase (iNOS) inhibitor 1400W, morphine or the vehicles. Both meniscotomy and meniscectomy groups displayed persistent and significant increase in pain behavior as compared to controls, being significantly more severe in the former. Cell influx was more intense in the meniscotomy as compared to the meniscectomy group. Structural damage at the tibia, but not at the femur, was also more severe in the meniscotomy group. Indomethacin and 1400W partially but significantly reduced pain whereas morphine abrogated pain behavior in meniscotomized mice.
Does keratinocyte growth factor ameliorate mucosal injury in an experimental model of colitis in rats?	Keratinocyte growth factor (KGF) is known to enhance tissue repair in the skin; however, its role in the gastrointestinal tract is largely unknown. The aim of this study was to evaluate the effects of exogenous KGF in an experimental model of colitis in rats. KGF was administered before or after induction of colitis with 2,4,6-trinitrobenzenesulfonic acid/ethanol. In the first two study groups, KGF (5 mg/kg) was administered intraperitoneally 24 hours and 1 hour before induction of colitis; animals were killed 8 hours (n=10) and 1 week (n=10) after injury. In subsequent study groups, KGF or vehicle treatment was begun 24 hours after the induction of colitis at doses of 5 (n=20), 1 (n=10), and 0.1 (n=10) mg/kg intraperitoneally and continued once daily for 1 week. Colonic tissue samples were evaluated macroscopically and microscopically for mucosal injury and assayed for myeloperoxidase activity. Administration of KGF after but not before induction of colitis significantly ameliorated tissue damage. Macroscopic necrosis and microscopic ulcerations were reduced by 40%-50% at KGF doses of 1 and 5 mg/kg.	The site of metabolism of prostate specific antigen (PSA) was determined. In a prospective study, during clinically indicated left and right heart catheterizations for various cardiac diseases in 12 men (mean age 62.5 +/- 8.3 years, standard deviation), selective blood samples were obtained from the infra-renal, infra-hepatic and supra-hepatic inferior vena cava, renal vein, superior vena cava, pulmonary artery and femoral artery. Mean PSA concentration was calculated for all vascular sites. Using a paired Student t test, the mean difference between the afferent and efferent PSA concentrations across the renal, hepatic, pulmonary and pelvic circulation was calculated. The hepatic gradient between the infra-hepatic and suprahepatic inferior vena cava showed the greatest decrease (0.11 +/- 0.16 ng./ml. or 8.3%) in PSA concentration and was statistically significant (p = 0.04). A smaller decrease across the pulmonary circulation was statistically insignificant. No decrease in the PSA concentration was noted across the renal circulation. The PSA concentration increased significantly (0.19 +/- 0.18 ng./ml. or 16.3%, p = 0.003) across the pelvic circulation, confirming the release of PSA from the prostate.
Does smokeless tobacco increase aneuploidy in oral HPV16 E6/E7-transformed keratinocytes in vitro?	The scope of this work was to study synergism between human papillomavirus (HPV) infection and tobacco in vitro, both known to be independent risk factors for oral cancer. HPV-positive and HPV-negative oral keratinocytes and oral HPV-negative fibroblasts were exposed to smokeless tobacco extract (STE) prepared from the Scandinavian (STE1) and US-type (STE2) snuff. Cell cycle profiles were determined with flow cytometry, and HPV E6/E7 mRNA expression in HPV-positive cells was assayed using RT-qPCR. The exposure of HPV-positive keratinocytes with STE2 increased the number of aneuploid cells from 27% to 80% of which 44% were in S-phase, while none of the diploid cells were in S-phase. The changes after STE1 exposure were less than seen after STE2: from 27% to 31% of which 34% were in S-phase. STE had no effect on HPV16 E6/E7 expression in HPV-positive keratinocytes. In oral spontaneously transformed, HPV-negative keratinocytes, the number of aneuploid cells at G2-M stage increased after STE1 and STE2 exposure from 3% to 9% and 7%, respectively. In HPV-negative oral fibroblasts, the number of cells at G2-M phase increased from 11% to 21% after STE1 and 29% after STE2 exposure.	Certain aspects of total knee arthroplasty (TKA) in severely and morbidly obese (SMO) patients (BMI ≥ 35 kg/m(2)) remain controversial. This study aimed to assess the duration of TKA surgery and hospital stay in relation to patients' BMI. Three operative times during TKA surgery were recorded: tourniquet time, to determine surgical difficulty, total surgical time, to assess the difficulty of achieving anaesthesia, and time in the surgical area, to assess patient management in the surgical area. Length of hospital stay was also calculated. Data were collected prospectively from consecutive patients and were recorded in a database for retrospective analysis. Data were obtained from 922 consecutive patients undergoing TKA. The non-obese group comprised 418 patients (45.3%), obese group Class I 331 (36%), and the SMO group (Class II-III) 173 (18.7%). Mean tourniquet time was 53 min, mean total surgical time was 84 min, and mean time in the surgical area was 132 min. There were no differences according to BMI group. Median length hospital stay (LHS) was 6 days in all patients regardless of BMI. Factors that significantly prolonged LHS were ASA III-IV and pre-operative haemoglobin between 12 and 13 g/dl.
Is urine NGAL useful in the clinical evaluation of renal function in the early course of acute pancreatitis?	Acute Kidney Injury (AKI) is a serious early complications in patients with acute pancreatitis (AP) that signifcantly increases mortality rates compared to patients without AKI. The early diagnosis of AKI during its treatable phases and implementation of appropriate treatment protocols can improve outcomes for this group of patients. A promising biomarker for AKI is neutrophil gelatinase-associated lipocalin (NGAL). This study evaluated the diagnostic value of NGAL concentrations in serum and in urine for patients developing AKI as an early complication of AP compared to AP patients without AKI. The study group composed of 65 patients (34 men and 31 women) with a mean age of 62.2 ± 16 years with AP and hospitalized in the Surgery Department of the Direct Hospital in Sucha Beskidzka, Poland between January and December 2014. Serum NGAL (sNGAL) levels were measured with the BioVendor ELISA kit, and urine NGAL (uNGAL) with the Abbott ARCHITECT Analyzer. In the early phase of AP, 11 patients (17%) developed AKI, including 10 patients with stage 1 and one with stage 2. AKI was associated with more severe AP, higher BISAP scores, the need for more intensive treatment, longer hospital stays and higher mortality. Both serum and urine NGAL concentrations were signifcantly higher in patients with AKI throughout the study and signifcantly predicted AKI in simple and multiple logistic regression adjusted for age, sex and comorbidities. Serum and urine NGAL concentrations were signifcantly correlated with levels of serum urea, creatinine, urine albumin, and the maximum change in serum creatinine. Serum and urine NGAL levels also correlated positively with direct neutrophil counts and CRP concentrations throughout the study.	There is evidence that the inner retina is involved in eye growth control processes and the development of myopia. We sought to investigate the response dynamics of the inner retina of adult emmetropes and myopes using the global flash multifocal electroretinogram (mfERG) paradigm. Fourteen myopes and 10 emmetropic subjects (mean age: 21.0+/-2.8 years) underwent mfERG testing using VERIS 5.1.5X. The global flash stimulus array consisted of 103-scaled hexagons which flickered according to a pseudorandom binary m-sequence (2(13)-1). The stimulation sequence was modified by inserting three frames, a dark frame, a global (full screen) flash, and another dark frame. The amplitude and implicit time of the two distinct waveform features, an early direct component (DC) and a later induced component (IC) of the first-order kernel were analyzed. Retinal responses were averaged over rings of increasing eccentricity, or into nasal and temporal hemifields. There was a significant correlation between the DC and IC response amplitude and myopic refractive error, i.e., the greater the myopic error, the greater the response amplitude. However, when comparing between the two refractive error groups, DC and IC response amplitudes of emmetropes and myopes were similar, even after compensating for the effect of axial length. There were no significant differences in implicit times of the DC and IC in emmetropes and myopes.
Does expression of Tiam1 and VEGF-C correlate with lymphangiogenesis in human colorectal carcinoma?	To investigate the relationship between Tiam1 and lymphangiogenesis in human colorectal carcinoma (CRC) tissues, as well as the expression of VEGF-C in a CRC cell line (HCT116) after knockdown of the Tiam1 gene with RNA interference (RNAi). In the specimens of CRC tissue, the positivity rate of Tiam1 and VEGF-C was 84% and 58%, respectively. The positivity rate of VEGF-C in the Tiam1 positive group (64.3%) was significantly higher than that in the Tiam1 negative group (25.0%). The LMVD in the Tiam1 positive group (11.35 +/- 3.34) was significantly higher than that in the Tiam1 negative group (7.38 +/- 2.27). In addition, the expression of the Tiam1 gene was efficiently blocked by RNAi. Downregulation of Tiam1 gene expression significantly suppressed HCT116 cell growth in vitro. Compared with untransfected HCT116 cells, HCT116 cells transfected with pGenesil-1-Tiam1 plasmids showed a significant decrease in the expression of VEGF-C. The expressions of Tiam1, Rac1, VEGF-C and Podoplanin in 50 samples of CRC were detected by immunohistochemical analysis. The lymph microvessel density (LMVD) in Podoplanin positive specimens was evaluated. The results were analyzed statistically to investigate the correlation of Tiam1, VEGF-C, lymph node metastasis and other clinicopathological parameters. An shRNA eukaryotic expression vector against Tiam1 gene was constructed and transfected into HCT116 cells. The expression of Tiam1 gene was assessed by RT-PCR and western blot analysis.	Alkaline phosphatase (AP) attenuates inflammatory responses by lipopolysaccharide detoxification and may prevent organ damage during sepsis. To investigate the effect of AP in patients with severe sepsis or septic shock on acute kidney injury. A multicenter double-blind, randomized, placebo-controlled phase IIa study (2:1 ratio). Thirty-six intensive care unit patients (20 men/16 women, mean age 58 +/- 3 years) with a proven or suspected Gram-negative bacterial infection, >or=2 systemic inflammatory response syndrome criteria (<24 hours), and <12 hours end-organ dysfunction onset were included. An initial bolus intravenous injection (67.5 U/kg body weight) over 10 minutes of AP or placebo, followed by continuous infusion (132.5 U/kg) over the following 23 hours and 50 minutes. Median plasma creatinine levels declined significantly from 91 (73-138) to 70 (60-92) micromol/L only after AP treatment. Pathophysiology of nitric oxide (NO) production and subsequent renal damage were assessed in a subgroup of 15 patients. A 42-fold induction (vs. healthy subjects) in renal inducible NO synthase expression was reduced by 80% +/- 5% after AP treatment. In AP-treated patients, the increase in cumulative urinary NO metabolite excretion was attenuated, whereas the opposite occurred after placebo. Reduced excretion of NO metabolites correlated with the proximal tubule injury marker glutathione S-transferase A1-1 in urine, which decreased by 70 (50-80)% in AP-treated patients compared with an increase by 200 (45-525)% in placebo-treated patients.
Are interleukin-8 concentrations elevated in peritoneal fluid of women with endometriosis?	To investigate the presence of interleukin-8 (IL-8), a macrophage-derived angiogenic factor, in peritoneal fluid (PF) of women with and without endometriosis. Case-control study. University hospital. Eighteen women with laparoscopic findings of mild to severe endometriosis, and nine women with no visual evidence of pelvic pathology. Peritoneal fluid IL-8 levels were determined using an ELISA. Interleukin-8 concentrations were compared among women with and without endometriosis. Correlation between PF IL-8 concentration and endometriosis stage was investigated. Interleukin-8 was detectable in the PF of a majority of women (67%). Interleukin-8 concentrations were higher in the PF of women with endometriosis than in matched normal controls. A significant correlation between PF IL-8 concentration and endometriosis stage was noted.	Activation of the NOP receptor by its endogenous ligand nociceptin/orphanin FQ reduces ethanol intake in genetically selected alcohol preferring Marchigian Sardinian alcohol preferring (msP) rats. Here we evaluated whether buprenorphine, a partial agonist at micro-opioid and NOP receptors, would reduce ethanol consumption in msP rats via activation of NOP receptors. Marchigian Sardinian alcohol preferring rats trained to drink 10% alcohol 2 hours/day were injected with buprenorphine (.03, .3, 3.0, or 6.0 mg/kg intraperitoneally [IP]) 90 min before access to ethanol. Similar to prototypical micro-agonists, the two lowest doses of buprenorphine significantly increased ethanol consumption (p < .01); in contrast, the two highest doses reduced it (p < .05). Pretreatment with naltrexone (.25 mg/kg IP) prevented the increase of ethanol intake induced by .03 mg/kg of buprenorphine (p < .001) but did not affect the inhibition of ethanol drinking induced by 3.0 mg/kg of buprenorphine. Conversely, pretreatment with the selective NOP receptor antagonist UFP-101 (10.0 or 20.0 microg/rat) abolished the suppression of ethanol drinking by 3.0 mg/kg of buprenorphine.
Does porcine liver vascular bed in Biodur E20 corrosion cast?	Pigs are frequently used as animal models in experimental medicine. To identify processes of vascular development or regression, vascular elements must be recognised and quantified in a three-dimensional (3D) arrangement. Vascular corrosion casts enable the creation of 3D replicas of vascular trees. The aim of our study was to identify suitable casting media and optimise the protocol for porcine liver vascular corrosion casting. Mercox II® (Ladd Research, Williston, Vermont, USA) and Biodur E20® Plus (Biodur Products, Heidelberg, Germany) were tested in 4 porcine livers. The resins (volume approximately 700 mL) were injected via the portal vein. Corrosion casts were examined by macro-computed tomography, micro-computed tomography and scanning electron microscopy. For hepatectomies, the operating protocol was optimised to avoid gas or blood clot embolisation. We present a protocol for porcine liver vascular bed casting based on corrosion specimens prepared using Biodur E20® epoxy resin.	Little information exists about how cognitive impairment in multiple sclerosis (MS) patients impacts on their caregivers' health-related quality of life (HRQoL). The objective of this paper is to examine the extent to which cognitive impairment in MS patients contributes to caregivers' HRQoL. A total of 63 MS patients, 63 caregivers and 59 matched controls were recruited. Patients and controls underwent a neuropsychological assessment, including tests of working memory, speed of information processing, executive function, and verbal fluency. HRQoL of the caregivers was assessed by CAREQOL-MS. In logistic regression models, we adjusted for the effects of confounding variables. In these models, the dependent variable was the CAREQOL-MS (higher median of CAREQOL-MS (worse HRQoL) vs. lower median of CAREQOL-MS (better HRQoL) (reference)), and the independent variable was the impairment on each neuropsychological test vs. its integrity (reference). Cognitive impairment in MS patients was significantly associated with worse caregiver HRQoL (adjusted odds ratio (OR) = 3.10, 95% confidence interval (CI) = 1.07-11.55, p = 0.04). In secondary analyses in which each neuropsychological test was entered in the analyses separately, only Symbol Digit Modalities Test (a measurement of information processing speed) impairment (OR = 4.22, 95%, CI = 1.16-14.53, p = 0.03) was significantly associated with worse caregiver HRQoL.
Is the neovolcanic axis a barrier to gene flow among Aedes aegypti populations in Mexico that differ in vector competence for Dengue 2 virus?	Aedes aegypti is the main mosquito vector of the four serotypes of dengue virus (DENV). Previous population genetic and vector competence studies have demonstrated substantial genetic structure and major differences in the ability to transmit dengue viruses in Ae. aegypti populations in Mexico. Population genetic studies revealed that the intersection of the Neovolcanic axis (NVA) with the Gulf of Mexico coast in the state of Veracruz acts as a discrete barrier to gene flow among Ae. aegypti populations north and south of the NVA. The mosquito populations north and south of the NVA also differed in their vector competence (VC) for dengue serotype 2 virus (DENV2). The average VC rate for Ae. aegypti mosquitoes from populations from north of the NVA was 0.55; in contrast the average VC rate for mosquitoes from populations from south of the NVA was 0.20. Most of this variation was attributable to a midgut infection and escape barriers. In Ae. aegypti north of the NVA 21.5% failed to develop midgut infections and 30.3% of those with an infected midgut failed to develop a disseminated infection. In contrast, south of the NVA 45.2% failed to develop midgut infections and 62.8% of those with an infected midgut failed to develop a disseminated infection.	Systemic mastocytosis is a clonal myeloproliferative neoplasm associated with constitutional symptoms from mast cell mediated chemical and cytokine release. According to the literature, Ruxolitinib, a JAK1/JAK2 inhibitor, has been shown to reduce symptoms related to proinflammatory cytokine release in other myeloproliferative neoplasms. Here we present a case using Ruxolitinib for disabling constitutional symptoms despite complete bone marrow response in a patient with aggressive systemic mastocytosis. Assessment tools used to monitor symptoms in previously published Ruxolitinib trials were adopted to track symptom improvement and quality of life.
Do serum interferon-inducible protein 10 levels predict hepatitis B s antigen seroclearance in patients with chronic hepatitis B?	Hepatitis B s antigen (HBsAg) seroclearance is regarded as the optimal virological end-point. To investigate the dynamic changes in serum cytokine levels around the time of HBsAg seroclearance. This was a case-control study. Consecutive patients with chronic hepatitis B (CHB) who lost HBsAg were matched with those remained positive for HBsAg with same age, gender, HBeAg status and presence of cirrhosis in 1:2 ratio. Relevant serum cytokines [interleukin (IL)-2, IL-3, IL-4, IL-7, IL-9, IL-10, IL-12, IL-15, IL-21 interferon-γ, tumour necrosis factor-α (TNF-α), granulocyte macrophage colony-stimulating factor (GM-CSF) and interferon-inducible protein 10 (IP-10)] were assayed at the time (Year 0) and 3 years before (Year -3) HBsAg seroclearance. Seventy-one and 142 CHB patients who did and did not achieve HBsAg seroclearance were included. Mean age was 48 ± 11 years; 76% were male, 20% had positive HBeAg, 99 (46%) patients received anti-viral therapy, and mean baseline HBV DNA was 3.78 ± 2.28 log IU/mL vs. 4.36 ± 2.13 log IU/mL respectively (P = 0.05). In those who achieved HBsAg seroclearance, serum IL-15 and GM-CSF levels decreased significantly from Year -3 to Year 0 (P = 0.017 and 0.05 respectively). When compared to controls, only serum IP-10 level was significantly lower at Year 0 than at Year -3 in patients with HBsAg seroclearance. Lower serum IP-10 level at Year 0 was the only factor associated with HBsAg seroclearance. There was no correlation between serum IP-10 and HBsAg levels around the time of HBsAg seroclearance.	Functional stimulation is accompanied by increases in regional cerebral blood flow which exceed metabolic demands under normal circumstances, but it is unknown whether functional stimulation is beneficial or detrimental in the setting of acute ischemia. The aim of this study was to determine the effect of forepaw stimulation during temporary focal ischemia on neurological and tissue outcome in a rat model of reversible focal forebrain ischemia. Sprague-Dawley rats were prepared for temporary occlusion of the right middle cerebral artery (MCA) using the filament model. Cerebral blood flow in the MCA territory was continuously monitored with a laser-Doppler flowmeter. Subdermal electrodes were inserted into the dorsal forepaw to stimulate either the forepaw ipsilateral or contralateral to the occlusion starting 1 minute into ischemia and continuing throughout the ischemic period. A neurological evaluation was undertaken after 24 hours of reperfusion, and animals were then euthanized and brain slices stained with 2,3,5-triphenyltetrazolium chloride. Cortical and striatal damage was measured separately. The cortical and striatal infarct volumes were both significantly reduced in the contralateral stimulated group compared with the ipsilateral stimulated group (48% total reduction). There were no statistically significant differences in the neurobehavioral scores between the 2 groups, or in the laser-Doppler flow measurements from the MCA core.
Are igE and FcεRI highly expressed on innate cells in psoriasis?	Although elevated serum IgE levels have been reported in psoriasis, the role of IgE in psoriasis still needs to be clarified. To analyse serum total IgE levels in addition to the presence and distribution of IgE and FcεRI in psoriatic lesions, and to investigate alteration of IgE and FcεRI after successful systemic treatment. Total serum IgE levels were determined using enzyme-linked immunosorbent assay. The expression and localization of IgE and FcεRI was investigated using immunohistochemistry and double immunofluorescence. Elevated total serum IgE levels were found in 39% of patients with psoriasis. The levels of total serum IgE were significantly higher in male patients compared with female patients. Furthermore, total serum IgE levels decreased after successful systemic treatment. A positive correlation between IgE+ and FcεRI+ cells and a significant increase of these cells was found in psoriatic lesions when compared with normal skin. Interestingly, IgE+ and FcεRI+ cells decreased significantly after successful therapy with ustekinumab. IgE and FcεRI were coexpressed on mast cells, epidermal Langerhans cells, dermal dendritic cells, macrophages and a small number of neutrophils.	Restoring leaflet coaptation is the primary objective in repair of ischemic mitral regurgitation (IMR). The common practice of placing an undersized annuloplasty ring partially achieves this goal by correcting annular dilation; however, annular reduction has been demonstrated to exacerbate posterior leaflet tethering. Using a sheep model of IMR, we tested the hypothesis that posterior leaflet augmentation (PLA) combined with standard annuloplasty sizing increases leaflet coaptation more effectively than undersized annuloplasty alone. Eight weeks after posterobasal myocardial infarction, 15 sheep with 2+ or greater IMR underwent annuloplasty with either a 24-mm annuloplasty ring (24-mm group, n = 5), 30-mm ring (30-mm group, n = 5), or 30-mm ring with concomitant augmentation of the posterior leaflet (PLA group, n = 5). Using three-dimensional echocardiography, postrepair coaptation zone and posterior leaflet mobility were assessed. Leaflet coaptation length after repair was greater in the PLA group (4.1 ± 0.3 mm) and the 24-mm group (3.8 ± 0.5 mm) as compared with the 30-mm group (2.7 ± 0.6 mm, p < 0.01). Leaflet coaptation area was significantly greater in the PLA group (121.5 ± 6.6 mm(2)) as compared with the 30-mm group (77.5 ± 17.0 mm(2)) or the 24-mm group (92.5 ± 17.9 mm(2), p < 0.01). Posterior leaflet mobility was significantly greater in the PLA group as compared with the 30-mm group or the 24-mm group.
Do phospholipase A2 Group III and Group X Have Opposing Associations with Prognosis in Colorectal Cancer?	Although secretory phospholipase A2 (sPLA2) has been shown to be involved in various biological processes, its specific roles in sub-types of cancer development remain to be elucidated. We examined the expression of sPLA2 group III (GIII) in 142 patients with colorectal cancer using immunohistochemistry, and its correlation with clinicopathological features and outcomes. In addition, we examined the co-expression of sPLA2GIII and sPLA2GX using serial tissue sections to clarify the roles of both proteins in colorectal carcinogenesis. In 66 cases, diffuse staining of sPLA2GIII was seen; this was defined as the group with high expression. High expression was associated with a significantly higher rate of lymph node metastasis (p=0.02) and poorer survival (p=0.03) compared with low expression. Patients with low sPLA2GIII and high sPLA2GX expression had a significantly higher survival rate than those with high sPLA2GIII and low sPLA2GX expression (p=0.038).	We determined the effect of infusing the iron chelator deferoxamine complexed to hetastarch on the degree of lung dysfunction and systemic abnormalities produced by a severe smoke exposure. Adult sheep were given a smoke exposure under anesthesia that produced a peak carboxyhemoglobin between 40% and 45%. Twenty-eight sheep were studied; eight were given smoke alone and resuscitated with sufficient lactated Ringer's solution to maintain baseline hemodynamics. Seven sheep were given a bolus plus 1 ml/kg/hr of a 10% deferoxamine-hetastarch solution for resuscitation; five were given hetastarch alone. The response was compared with eight controls during a period of 24 hours. Smoke alone and smoke with hetastarch resulted in a shunt fraction of greater than 25% and a 50% decrease in compliance, severe airway inflammation, mucosal slough, atelectasis, and some alveolar edema. Increased lipid peroxides measured as malondialdehyde were present in airway fluid. In addition, oxygen consumption increased by 100% early after injury, net 24-hour positive fluid balance was almost 3 L, and a significant increase occurred in liver lipid peroxidation. The group given deferoxamine had a significantly attenuated lung response, with only modest airway damage lung dysfunction, and minimal systemic changes including a net positive fluid balance of just over 1L and no liver lipid peroxidation.
Is in-room display of day and time patient anticipated to leave hospital : a `` discharge appointment ''?	We learned from a focus group that many patients find discharge to be one of the least satisfying elements of the hospital experience. Patients cited insufficient communication about the day and time of the impending discharge as a cause of dissatisfaction. In partnership with the Institute for Healthcare Improvement, Improvement Action Network collaborative, we tested the practicality of an in-room "discharge appointment" (DA) display. Eight inpatient care units in 2 hospitals at an academic medical center (Mayo Clinic, Rochester, MN). DA displayed on a specially designed bedside dry-erase board. The primary outcome was the proportion of discharged patients who had been given a DA, including same-day DAs. Secondary outcomes were (1) the proportion of DAs scheduled before the actual dismissal day and (2) the timeliness of the actual departure compared with the DA. During the 4-month period, 2046 patients were discharged. Of those, 1256 patients (61%) were given a posted DA, of which 576 (46%) were scheduled at least a day in advance and 752 (60%) departed from the care unit within 30 minutes of the appointed time.	To investigate the eff ect of intestinal trefoil factor (ITF) on the transcriptional activity of ITF promoter and to explore the regulatory mechanism of Janus kinase/signal transducers and activators of transcription (JAK/STAT) on ITF promoter. The 5' flanking sequence of the ITF gene was cloned from human whole blood genomic DNA by PCR. ITF promoter fragment was cloned and inserted into the pGL3-Basic vector to construct recombinant vector. ITF promoter vector was stimulated with ITF at various concentrations and the luciferase activity was measured. The JAK-STAT3 signal transduction pathway was then blocked by a specific inhibitor AG490 to determine the signal pathway involved in ITF promoter activity. Restriction endonuclease analysis and DNA sequencing confirmed that the recombinant plasmid, containing ITF promoter, was constructed successfully. After transient transfection, the activity of ITF promoter was increased significantly in the presence of ITF (P<0.05). Blockage of the JAK-STAT3 signal transduction pathway with AG490 significantly reduced the ITF promoter activity (P<0.05).
Does inhibition of cyclin-dependent kinases by olomoucine and roscovitine reduce lipopolysaccharide-induced inflammatory responses via down-regulation of nuclear factor kappaB?	Initiation and maintenance of pro-inflammatory reactions elicited by bacterial lipopolysaccharide and/or cytokines in the macrophage lineage have been reported to play a crucial role in acute and chronic pathogenic effects. Whether pro-inflammatory responses triggered by lipopolysaccharide in growth arrested cells differ from those in proliferating cells remains unanswered. Olomoucine and roscovitine are cyclin-dependent kinase (CDK) inhibitors that prevent progression through the cell cycle. After treatment with CDK inhibitors, expression of pro-inflammatory genes was analysed by reverse transcriptase-polymerase chain reaction. Protein levels of inducible nitric oxide synthase (iNOS) and nuclear factor kappaB (NF-kappaB) were determined by Western blotting. Promoter activity of iNOS was measured by the luciferase activity assay. In this study we have demonstrated that both olomoucine and roscovitine inhibit cell proliferation and diminish nitric oxide production and cytokine gene expression, in lipopolysaccharide-stimulated murine RAW264.7 macrophages. In addition, olomoucine reduces iNOS promoter activity and alleviates NF-kappaB transcription activation. After co-transfection with E2F1 interference RNA, suppression of lipopolysaccharide-mediated iNOS promoter activity and NF-kappaB activation was observed. Furthermore, we demonstrated that olomoucine-induced growth arrested cells reduce expression of the p65 subunit of NF-kappaB.	We assessed the feasibility of a novel urinary test for prostate cancer based on the presence of alpha methylacyl coenzyme A racemase (AMACR) protein in voided urine specimens obtained after prostate biopsy. Clean catch voided urine specimens were prospectively collected from 26 consecutive men immediately after transrectal ultrasound guided prostate biopsy for suspected malignancy. The presence of AMACR was evaluated in a blinded manner by Western blot analysis and correlated with biopsy results and patient clinical information. AMACR was detected in the urine in 18 of 26 patients (69%). AMACR was detected in all 12 patients with biopsy confirmed adenocarcinoma of the prostate (100% sensitivity, 95% CI 75 to 100), in 5 of 12 with no evidence of cancer on biopsy (58% specificity, 95% CI 29 to 78) and in 1 of 2 (50%, 95% CI 3 to 80) with atypia on biopsy. Overall AMACR detection was associated with cancer status by prostate biopsy in 21 of 26 patients (86%).
Does reference range for serum and salivary testosterone in young men of Mediterranean region?	The interassay variability found in the measurement of testosterone (T) levels warrants the need for laboratories to validate their methods to establish trustworthy cut-off points for diagnosis of male hypogonadism. The aims of this study were to validate measurement of total T (TT) at our laboratory in order to obtain reference ranges for TT, calculated free T (CFT), calculated bioavailable T (CBT), and salivary T (ST) in healthy young men from the Mediterranean region, and to evaluate the potential clinical value of ST by establishing its correlation with serum T. An observational, cross-sectional study with sequential sampling. men aged 18-30 years with body mass index (BMI)<30. chronic diseases, hepatic insufficiency or use of drugs altering circulating T levels. Main outcome measures TT (chemiluminescent immunoassay UniCell DXI 800 [Access T Beckman Coulter]), CFT and CBT (Vermeulen's formula), and ST (radioimmunoassay for serum TT modified for saliva [Coat-A-Count, Siemens]). Descriptive statistical analyses and correlation by Spearman's rho (SPSS 19.0 Inc., Chicago) were used. One hundred and twenty-one subjects aged 24±3.6 years with BMI 24±2.5 kg/m(2) were enrolled. Hormone study: TT, 19±5.5 nmol/L (reference range [rr.] 9.7-33.3); CFT, 0.38 nmol/L (rr. 0.22-0.79); CBT, 9.7 nmol/L (rr. 4.9-19.2); and ST, 0.35 nmol/L (rr. 0.19-0.68). Correlation between ST and CFT was 0.46.	Morphogenesis of the zebrafish neural tube requires the coordinated movement of many cells in both time and space. A good example of this is the movement of the cells in the zebrafish neural plate as they converge towards the dorsal midline before internalizing to form a neural keel. How these cells are regulated to ensure that they move together as a coherent tissue is unknown. Previous work in other systems has suggested that the underlying mesoderm may play a role in this process but this has not been shown directly in vivo. Here we analyze the roles of subjacent mesoderm in the coordination of neural cell movements during convergence of the zebrafish neural plate and neural keel formation. Live imaging demonstrates that the normal highly coordinated movements of neural plate cells are lost in the absence of underlying mesoderm and the movements of internalization and neural tube formation are severely disrupted. Despite this, neuroepithelial polarity develops in the abnormal neural primordium but the resulting tissue architecture is very disorganized.
Are hypoalbuminaemia and impaired renal function associated with increased anticholinergic drug prescribing?	A higher anticholinergic risk score (ARS) is associated with an increased risk of anticholinergic adverse effects in elderly patients. It is unknown whether factors other than the use of anticholinergic drugs determine the ARS. A comprehensive medical record review was conducted in 155 consecutive hospitalised patients (median age 79.0 years, interquartile range 66.0-86.0). Information was collected on: demographics; clinical characteristics (including medications and their doses); history of anticholinergic-induced adverse effects; and biochemical markers of hepatic and renal function (serum albumin concentrations and estimated glomerular filtration rate, eGFR). The ARS was calculated for each patient using a standard scoring approach and Poisson regression was used for identifying variables associated with the ARS. Patients with an ARS >or= 3 had a lower eGFR (p = 0.012) and were receiving more non-anticholinergic drugs (p < 0.001) than patients with an ARS < 3. In addition to being prescribed more anticholinergic drugs, patients with ARS >or= 3 were prescribed high doses of these drugs more often than patients with ARS < 3 (41.3% vs. 26.9%, p = 0.034). A higher number of non-anticholinergic drugs (p < 0.001), a lower serum albumin concentration (p = 0.014), and a lower eGFR (p = 0.012) were independently associated with a higher ARS.	Pathogenic mycobacteria such as M. tuberculosis, M. bovis or M. leprae are characterised by their extremely slow growth rate which plays an important role in mycobacterial virulence and eradication of the bacteria. Various limiting factors influence the generation time of mycobacteria, and the mycobacterial DNA-binding protein 1 (MDP1) has also been implicated in growth regulation. Our strategy to investigate the role of MDP1 in mycobacterial growth consisted in the generation and characterisation of a M. bovis BCG derivative expressing a MDP1-antisense gene. The expression rate of the MDP1 protein in the recombinant M. bovis BCG containing the MDP1-antisense plasmid was reduced by about 50% compared to the reference strain M. bovis BCG containing the empty vector. In comparison to this reference strain, the recombinant M. bovis BCG grew faster in broth culture and reached higher cell masses in stationary phase. Likewise its intracellular growth in mouse and human macrophages was ameliorated. Bacterial clumping in broth culture was reduced by the antisense plasmid. The antisense plasmid increased the susceptibility of the bacteria towards Ampicillin. 2-D protein gels of bacteria maintained under oxygen-poor conditions demonstrated a reduction in the number and the intensity of many protein spots in the antisense strain compared to the reference strain.
Do [ Evaluation of effectiveness and safety of a new hydroxyethyl starch used in resuscitation of burn shock ]?	To evaluate the effectiveness and safety of hydroxyethyl starch (HES 130/ 0.4, 60 g/L) in resuscitation during shock stage of burns. Sixty-six burn patients who were admitted to hospital within 2 hours after burn injury requiring fluid resuscitation were enrolled into this study, and they were randomized into HES( n = 33, with HES as a component of fluid resuscitation) and plasma (P, n = 33, with plasma as a component of fluid resuscitation) groups. HES or plasma was given as colloid within 48 postburn hours (PBH), and only albumin [( 111 +/- 4) , ( 105 +/- 5 ) g for each group] were given to the patients during 3 to 7 postburn days (PBD). Heart rate, blood pressure, central venous pressure (CVP) , urine output per hour were measured, gain/loss of body fluid during the first and second 24 PBH were recorded, serum total protein, albumin, hemoglobin( Hb) , prothrombin time (PT) , fibrinogen; platelet ( PLT) , as well as liver and renal function, allergy and bleeding tendency were determined and observed at corresponding time-points. There were no obvious differences in heart rate, blood pressure, CVP and urine output per hour within 24 PBH between the two groups (P > 0.05). Also there was no difference in gain/loss of body fluid during the first and second 24 PBH. The content of hemoglobin on 1 ,3, 7,14 PBD ,and the PT, the content of fibrinogen, the number of PLT on 1,3,14 PBD also exhibited no difference between the two groups (P > 0.05). The serum contents of total protein and albumin in HES group were [(31 +/- 3) g/L, (30 +/- 3)g/L ] on 1 PBD, and [(20.4 +/- 3.6) g/L, (18.4 +/-2.3) g/L] on 3 PBD, which were obviously lower than those in P group [(45 +/- 4) g/L, (39 +/- 3) g/L on 1 PBD, and 1 (24.5 +/- 4.3) g/L, (21.3 +/- 3.9) g/L) on 3 PBD, (P <0. 01). Though the serum content of albumin on 7 PBD was similar in the two groups (P > 0.05), the serum total protein in HES group (40 +/- 4) g/L was markedly lower than that in P group [(45 +/- 4) g/L, P < 0.01] . Within 7 PBD, no abnormal bleeding was found in the two groups, and the liver function and renal function were similar. There were 4 cases showing allergic reaction in plasma group while none in HES group.	Given evidence from genetic studies, we hypothesized that there may be a shared component to the role of myeloid function in Parkinson and Alzheimer disease (PD and AD) and assessed whether PD susceptibility variants influenced protein expression of well-established AD-associated myeloid genes in human monocytes. We repurposed data in which AD-related myeloid proteins CD33, TREM1, TREM2, TREML2, TYROBP, and PTK2B were measured by flow cytometry in monocytes from 176 participants of the PhenoGenetic Project (PGP) and Harvard Aging Brain Study. Linear regression was used to identify associations between 24 PD risk variants and protein expression. The 2 cohorts were meta-analyzed in a discovery analysis, and the 4 most strongly suggestive results were validated in an independent cohort of 50 PGP participants. We discovered and validated an association between the PD risk allele rs12456492(G) in the RIT2 locus and increased CD33 expression (p joint = 3.50 × 10(-5)) and found strongly suggestive evidence that rs11060180(A) in the CCDC62/HIP1R locus decreased PTK2B expression (p joint = 1.12 × 10(-4)). Furthermore, in older individuals, increased CD33 expression on peripheral monocytes was associated with a greater burden of parkinsonism (p = 0.047), particularly bradykinesia (p = 6.64 × 10(-3)).
Are gender differences in scalp hair growth rates maintained but reduced in pattern hair loss compared to controls?	Hair loss is related to follicular density, programmed regrowth and hair productivity. The dissatisfaction with hair growth in patients experiencing hair loss might be due to slower linear hair growth rate (LHGR). LHGR and hair diameter was evaluated in Caucasian controls and patients with patterned hair loss employing the validated non-invasive, contrast-enhanced-phototrichogram with exogen collection. We evaluated 59,765 anagen hairs (controls 24,609, patients 35,156) and found thinner hairs grew slower than thicker hairs. LHGR in normal women was generally higher than in normal men. LHGR correlates with hair diameter (P < 0.006) and global thinning is associated with slower growth rates. Compared with hair of equal thickness in controls, subjects affected with patterned hair loss showed reduced hair growth rates, an observation found in both male and female patients. Males with pattern hair loss showed further reduction in growth rates as clinical severity worsened. However, sample size limitations prevented statistical evaluation of LHGR in severely affected females.	Reactive oxygen species (ROS), including superoxide anion radical, induce chronic risk of oxidative damage to many cellular macromolecules resulting in damage to cells. Superoxide dismutases (SODs) catalyze the dismutation of superoxide to oxygen and hydrogen peroxide and are a primary defense against ROS. Vibrio parahaemolyticus, a marine bacterium that causes acute gastroenteritis following consumption of raw or undercooked seafood, can survive ROS generated by intestinal inflammatory cells. However, there is little information concerning SODs in V. parahaemolyticus. This study aims to clarify the role of V. parahaemolyticus SODs against ROS. V. parahaemolyticus SOD gene promoter activities were measured by a GFP reporter assay. Mutants of V. parahaemolyticus SOD genes were constructed and their SOD activity and resistance to oxidative stresses were measured. Bioinformatic analysis showed that V. parahaemolyticus SODs were distinguished by their metal cofactors, FeSOD (VP2118), MnSOD (VP2860), and CuZnSOD (VPA1514). VP2118 gene promoter activity was significantly higher than the other SOD genes. In a VP2118 gene deletion mutant, SOD activity was significantly decreased and could be recovered by VP2118 gene complementation. The absence of VP2118 resulted in significantly lowered resistance to ROS generated by hydrogen peroxide, hypoxanthine-xanthine oxidase, or Paraquat. Furthermore, both the N- and C-terminal SOD domains of VP2118 were necessary for ROS resistance.
Does microRNA-30a promote chondrogenic differentiation of mesenchymal stem cells through inhibiting Delta-like 4 expression?	MicroRNAs (miRNAs) play important roles in chondrogenic differentiation of mesenchymal stem cells (MSCs). However, the regulation of miR-30a during such process has not yet been well understood. The aim of the study was to investigate the effects of miR-30a on chondrogenic differentiation of MSCs and explore the underlying mechanisms. MSCs were isolated from rat bone marrow, and their immunophenotypes and multilineage differentiation potentials were identified. MiR-30a mimics or inhibitor were transfected into rat MSCs and SW1353 cells, respectively, and then the effects of miR-30a on chondrogenic differentiation were detected. The predicted target gene Delta-like 4 (DLL4, a ligand of the Notch signaling family) was verified by luciferase reporter assay, quantitative real time PCR and western blot. MiR-30a was significantly up-regulated during chondrogenic differentiation of rat MSCs. Additionally, transfection of miR-30a mimics remarkably promoted the differentiation of rat MSCs into chondrocytes as evidence by the notably increased mRNA and protein expression levels of chondrogenic markers Collagen II and aggrecan as well as the enhanced alcian blue staining intensity, whereas inhibition of miR-30a obviously suppressed such process. Furthermore, during chondrogenesis, DLL4 expression was found to significantly decrease at both mRNA and protein levels, which was negatively regulated by miR-30a through directly targeting the 3'UTR of DLL4.	To investigate the effect of cisapride, a relatively new prokinetic agent, on gastric emptying in critically ill patients. Prospective, randomized, controlled study. Adult medical/surgical intensive care unit in a university hospital. Twenty-one consecutively enrolled patients, requiring prolonged mechanical ventilation and enteral feeding. Patients were randomized to receive either no cisapride or 10 mg of cisapride four times daily, which was added to a standard enteral nutrition feeding protocol. Gastric emptying was evaluated by daily measurements of gastric residue and on days 5 through 7 by bedside scintigraphy. Normal values for gastric clearance of a tracer-labeled test meal and for measurements obtained in the supine position were determined in ten healthy volunteers. The mean time at which 50% of the technetium 99m-labeled test meal was eliminated from the stomach (T 1/2) in this control group was 31 +/- 15 mins. In ten critically ill patients (enteral nutrition group), gastric emptying was markedly delayed after 5 to 7 days of enteral feeding (mean T 1/2 = 78 +/- 40 mins; p < .002 as compared with the control group). In contrast, patients treated with cisapride (cisapride group) showed an accelerated gastric emptying (mean T 1/2 = 18 +/- 7 mins; p > .05 as compared with controls; p < .005 as compared with enteral nutrition group). The mean gastric residue over a 1-wk period was also significantly lower in the cisapride group than in the enteral nutrition group (17.7 +/- 8.9 vs. 94.5 +/- 33.4 mL; p < .001).
Does physician disclosure of healthy personal behaviors improve credibility and ability to motivate?	While some studies have shown that physicians with healthy personal habits are especially likely to discuss prevention with their patients, to our knowledge no one has published information testing whether physician credibility and patient motivation to adopt healthier habits are enhanced by physician's disclosures of their own healthy behaviors. Two brief health education videos about improving diet and exercise were produced and shown to subjects (n1 = 66, n2 = 65) in an Emory University general medical clinic waiting room in Atlanta, Ga. In one video, the physician revealed an additional half minute of information about her personal healthy dietary and exercise practices and had a bike helmet and an apple visible on her desk (physician-disclosure video). In the other video, discussion of personal practices and the apple and bike helmet were not included (control video). Viewers of the physician-disclosure video considered the physician to be generally healthier, some-what more believable, and more motivating than did viewers of the control video. They also rated this physician to be specifically more believable and motivating regarding exercise and diet (P < or = .001).	IQ-domain GTPase-activating protein 1 (IQGAP1) binds to Dishevelled (Dvl) and functions as a modulator of Dvl nuclear localization in Xenopus embryos. However, the relationship between IQGAP1 and Dvl in tumor tissues is unclear. We used immunohistochemistry to assess the expressions of IQGAP1 and Dvl in a cohort of 111 non-small cell lung cancer (NSCLC) patients. Association of their localization expressions with clinicopathological factors was also analyzed. The positive rate of IQGAP1 in primary tumors was 48.6% (54/111) for its cytoplamic expression, 9.0% (10/111) for nuclear expression and 31.5% (35/111) for membranous expression; the positive rate of Dvl was 65.8% (73/111) for cytoplamic expression, 9.9% (11/111) for nuclear expression and 10.8% (12/111) for membranous expression. Coexpression rate of IQGAP1 and Dvl was 77.8% (42/54) in the cytoplasm, 80.0% (8/10) in the nucleus and 8.6% (3/35) in the membrane. Coexpression of IQGAP1 and Dvl in the cytoplasm and nucleus were significantly correlated (P<0.05), but not in the membrane (P>0.05). The positive expression rates of cyclin D1 and c-myc were significantly higher in the group of IQGAP1 and Dvl coexpression in the nucleus than that in the cytoplasm. Coexpression rate of IQGAP1 and Dvl in the cytoplasm and nucleus was significantly higher in lymph nodal metastases (63.3%, 19/30) than in primary growths (38.3%, 31/81), correlating with poor prognosis. Five-year survival time after resection in the group with their coexpression in the cytoplasm and nucleus was significantly lower than that with no coexpression (44.705±3.355 vs 58.403±2.543 months, p<0.05).
Is vein graft neointimal hyperplasia exacerbated by CXCR4 signaling in vein graft-extrinsic cells?	Because vein graft neointimal hyperplasia engenders vein graft failure, and because most vein graft neointimal cells derive from outside the vein graft, we sought to determine whether vein graft neointimal hyperplasia is affected by activity of the CXC chemokine receptor-4 (CXCR4), which is important for bone marrow-derived cell migration. In congenic Cxcr4(-/+) and wild-type (WT) recipient mice, we performed interposition grafting of the common carotid artery with the inferior vena cava (IVC) of either Cxcr4(-/+) or WT mice to create four surgically chimeric groups of mice (n ≥ 5 each), characterized by vein graft donor/recipient: WT/WT; Cxcr4(-/+)/WT; WT/Cxcr4(-/+); and Cxcr4(-/+)/Cxcr4(-/+); vein grafts were harvested 6 weeks postoperatively. The agonist for CXCR4 is expressed by cells in the arterializing vein graft. Vein graft neointimal hyperplasia was reduced by reducing CXCR4 activity in vein graft-extrinsic cells, but not in vein graft-intrinsic cells: the rank order of neointimal hyperplasia was WT/WT ≈ Cxcr4(-/+)/WT > WT/Cxcr4(-/+) ≈ Cxcr4(-/+)/Cxcr4(-/+); CXCR4 deficiency in graft-extrinsic cells reduced neointimal hyperplasia by 39% to 47% (P < .05). Vein graft medial area was equivalent in all grafts except Cxcr4(-/+)/Cxcr4(-/+), in which the medial area was 60% ± 20% greater (P < .05). Vein graft re-endothelialization was indistinguishable among all three vein graft groups. However, the prevalence of medial leukocytes was 40% ± 10% lower in Cxcr4(-/+)/Cxcr4(-/+) than in WT/WT vein grafts (P < .05), and the prevalence of smooth muscle actin-positive cells was 45% ± 20% higher (P < .05).	Gastrin and pepsinogens reflect the functional state of the gastric mucosa. To evaluate whether serum gastrin and pepsinogens correlate with the different grades of severity of gastro-oesophageal reflux disease (GERD). In all, 388 patients with heartburn not taking any form of acid suppressive therapy were matched-controlled for age and gender and sub-classified into four groups: group 1 non-erosive reflux disease (NERD); group 2, erosive reflux disease (ERD) Los Angeles (LA) A and B, group 3, ERD LA C and D; group 4 Barrett's oesophagus (BO). Fasting serum was analysed for gastrin 17, pepsinogen I, pepsinogen II und Helicobacter pylori using specific EIA tests (GastroPanel; Biohit, Plc). Kruskal-Wallis test and analysis of variance. There was a significant difference among the four groups with respect for pepsinogen I, but not for pepsinogen II, the pepsinogen I pepsinogen II ratio, H. pylori serology and gastrin levels. Pepsinogen I was the lowest in NERD and the highest in BO (median 91.6, mean +/- standard deviation 106.2 +/- 51.6 vs. median 114.7, mean +/- standard deviation 130.4 +/- 70.6; P = 0.046). Pepsinogen I levels were higher in H. pylori positive subjects. After adjusting for H. pylori status, the differences in pepsinogen I across patient groups were no longer statistically significant (P = 0.298).
Are weight bearing radiographs necessary for measurement of polyethylene penetration in total hip prostheses : a radiostereometric study of 111 patients examined in weight-bearing and supine position?	Controversy exists as to whether polyethylene (PE) penetration of hip prostheses is underestimated when the measurements are made on radiographs obtained in supine position as compared to weight-bearing position. We examined 111 patients by radiostereometric analysis (RSA) in the supine and weight-bearing positions. The mean 3-D penetration was 0.68 mm (SD 0.58, range 0.04-3.05) for the supine position and 0.70 mm (SD 0.57, range 0.08-3.01) for the weight-bearing position. The correlation between supine and weight-bearing examinations was 0.99 (p < 0.001). The degree of penetration made no difference. There was no statistically significant difference as to whether the first examination was performed early, i.e. after 3 months, or after 12 months (p = 0.7).	The regulatory mechanisms of IL-5 gene transcription in human peripheral T cells are unclear because the transfection efficiency of plasmid constructs into nontransformed T cells is very low. Concanavalin A (ConA)-stimulated blastocytes derived from peripheral blood lymphocytes of asthmatic subjects were transiently transfected with the human IL-5 gene promoter/enhancer-luciferase gene construct, pIL-5 (-511)Luc, and cultured with THP-1 cells (human monocytoid cells) and anti-CD3 monoclonal antibody (mAb). IL-5 level in the culture medium was determined by an enzyme-linked immunosorbent assay. Transcriptional activity of the IL-5 gene was measured by luciferase reporter analysis. ConA-blast lymphocytes of asthmatic patients produced a significant amount of IL-5 upon combined stimulation with anti-CD3 mAb and THP-1 cells, but not with anti-CD3 mAb alone. Costimulation with anti-CD28 mAb also enhanced the anti-CD3 mAb- induced IL-5 production. Accordingly, luciferase activity induced by anti-CD3 mAb stimulation in pIL-5(-511)Luc-transfected ConA-blast lymphocytes was increased 1.9- and 3.4-fold by the addition of anti-CD28 mAb and THP-1 cells, respectively. Serial 5' deletion analysis of the reporter gene demonstrated that the cis-regulatory element located at -119 to -80 is critical for anti-CD3 mAb-induced IL-5 gene transcription.
Does glibenclamide attenuate myocardial injury by lipopolysaccharides in streptozotocin-induced diabetic mice?	Sepsis is a common disease that continues to increase in incidence in the world. Diseases, such as diabetes mellitus, may make the situation worse. Diabetic patients are at increased risk for common infections. This study was designed to investigate the role of glibenclamide on myocardial injury by lipopolysaccharides (LPS) in streptozotocin induced diabetic mice (STZ-mice). LPS was used to induce endotoxemia in STZ-mice. Heart rate and mean arterial pressure were measured by MPA-HBBS. Serum epinephrine level was measured by enzyme-linked immunosorbent assays (ELISA). Myocardial injury was examined by light and transmission electron microscope and TUNEL staining. Macrophage infiltration was measured by immunohistochemistry. Interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) levels in myocardial tissue and serum in STZ-mice, and in conditional medium of primary cultured peritoneal macrophages were determined by ELISA. Nalp3 and Caspase-1 protein levels were measured by Western blotting analysis. STZ administration decreased body weight and increased blood glucose in C57BL/6 mice. LPS injection caused decreases of heart rate and mean arterial pressure, and elevated serum epinephrine level in C57BL/6 mice. Compared with control mice without STZ treatment, LPS induced more severe myocardial injury and macrophage infiltration in STZ-mice, which was attenuated by pretreatment of glibenclamide. LPS stimulation enhanced the levels of IL-1β and TNF-α in both cardiac tissue and serum. Glibenclamide pretreatment significantly inhibited the serum levels of pro-inflammatory cytokines. Either high glucose or LPS increased the levels of IL-1β and TNF-α in the conditional medium of peritoneal macrophages. Glibenclamide treatment suppressed the increase of IL-1β level induced by high glucose and LPS. Furthermore, Nalp3 and Caspase-1 levels were markedly increased by high glucose plus LPS, and both proteins were significantly inhibited by glibenclamide treatment.	Plant genomes are populated by different types of repetitive elements including transposable elements (TEs) and simple sequence repeats (SSRs) that can have a strong impact on genome size and dynamic as well as on the regulation of gene transcription. At least two-thirds of the tomato genome is composed of repeats. While their bulk impact on genome organization has been recently revealed by whole genome assembly, their influence on tomato biology and phenotype remains largely unaddressed. More specifically, the effects and roles of DNA repeats on the maturation of fleshy fruits, which is a complex process of key agro-economic interest, still needs to be investigated comprehensively and tomato is arguably an excellent model for such study. We have performed a comprehensive annotation of the tomato repeatome to explore its potential impact on tomato genome composition and gene transcription. Our results show that the tomato genome can be fractioned into three compartments with different gene and repeat density, each compartment presenting contrasting repeat and gene composition, repeat-gene associations and different gene transcriptional levels. In the context of fruit ripening, we found that repeats are present in the majority of differentially methylated regions (DMRs) and thousands of repeat-associated DMRs are found in gene proximity including hundreds that are differentially regulated. Furthermore, we found that repeats are also present in the proximity of binding sites of the key ripening protein RIN. We also observed that some repeat families are present at unexpected high frequency in the proximity of genes that are differentially expressed during tomato ripening.
Do both Lewis and secretor status mediate susceptibility to rotavirus infections in a rotavirus genotype-dependent manner?	The live oral rotavirus (RV) vaccines have shown a reduced efficacy in Africa. Recent in vitro studies have shown binding of the RV surface protein (VP4) to histo-blood group antigens (HBGAs) in an RV genotype-dependent manner, suggesting them to be putative receptors for RV. The diversity of HBGA phenotypes in different ethnic populations, combined with prevalence/absence of specific RV genotypes, led us to hypothesize whether the genetic variations in HBGAs in a population limit susceptibility to certain RV genotypes, plausibly leading to reduced vaccine efficacy. Association between HBGAs status and susceptibility to RV P genotypes was investigated in children in Burkina Faso and Nicaragua. In total, 242 children with diarrhea in Burkina Faso and Nicaragua were investigated, 93 of whom were RV positive. In Burkina Faso, the P[8] RV strains (n = 27) infected only Lewis- and secretor-positive children (27/27; P < .0001), but no Lewis-negative children. In contrast, the P[6] strains (n = 27) infected predominantly Lewis-negative children (n = 18; P < .0001) but also Lewis-positive children, irrespective of their secretor status. The results from Nicaragua confirmed that all P[8]-infected children (n = 22) were secretor Lewis positive.	To assess the influence of vascular clamping and ischemia time on long-term post-operative renal function following partial nephrectomy (PN) for cancer in a solitary kidney. This is a retrospective study including 259 patients managed by PN between 1979 and 2010 in 13 centers. Clamping use, technique choice (pedicular or parenchymal clamping), ischemia time, and peri-operative data were collected. Pre-operative and last follow-up glomerular filtration rates were compared. A multivariate analysis using a Cox model was performed to assess the impact of ischemia on post-operative chronic renal failure risk. Mean tumor size was 4.0±2.3cm and mean pre-operative glomerular filtration rate was 60.8±18.9mL/min. One hundred and six patients were managed with warm ischemia (40.9%) and 53 patients with cold ischemia (20.5%). Thirty patients (11.6%) have had a chronic kidney disease. In multivariate analysis, neither vascular clamping (P=0.44) nor warm ischemia time (P=0.1) were associated with a pejorative evolution of renal function. Pre-operative glomerular filtration rate (P<0.0001) and blood loss volume (P=0.02) were significant independent predictive factors of long-term renal failure.
Does miRNA-26b inhibit cellular proliferation by targeting CDK8 in breast cancer?	MicroRNA-26b (miR-26b) has been reported to be down-regulated in a wide range of malignant tumors, However, the mechanism by which miR-26b is implicated in breast cancer tumorigenesis is incompletely understood. This study was undertaken to evaluate the expression pattern of miR-26b and characterize its biological role in human breast cancer. Reverse transcription-polymerase chain reaction (RT-PCR) was used to quantify the expression levels of miR-26b in breast cancer and adjacent non-cancerous breast tissues. MTT, colony formation assay and cell cycle assay were carried out to characterize the miR-26b function. Finally, to validate the target gene of miR-26b, luciferase reporter assay was employed, followed by RT-PCR and Western blot confirmation. Here, we found that miR-26b expression was relatively downregulated in breast cancer specimens (P<0.01). Overexpression of miR-26b dramatically suppressed cell proliferation, colony formation and induced G0/G1 cell cycle arrest of MDA-MB-231 and Mcf-7 cells. Luciferase assays revealed that miR-26b directly targeted the 3'UTR of CDK8. Overexpression of miR-26b led to the downregulation of CDK8 and β-catenin expression. Similarly, CDK8 knockdown by siRNA suppressed cell growth and subsequent β-catenin expression.	Enterotoxigenic Bacteroides fragilis has been associated with diarrheal disease, and the enterotoxin has a cytopathic effect on cultured HT-29 enterocytes. Experiments were designed to determine the effect of B. fragilis enterotoxin on bacteria-enterocyte interactions. Confluent HT-29 enterocytes were incubated for 1 hour with B. fragilis enterotoxin, followed by 1 hour of incubation with pure cultures of enteric bacteria, namely, Salmonella typhimurium (two strains), Listeria monocytogenes (three strains), Proteus mirabilis, Escherichia coli (three strains), and Enterococcus faecalis. Enterocyte viability was assessed using vital dyes, epithelial permeability was measured using transepithelial electrical resistance, enterocyte morphology and bacteria-enterocyte interactions were visualized using light and electron microscopy, and bacterial internalization was assessed using a quantitative culture of lysed enterocytes. B. fragilis enterotoxin did not affect enterocyte viability but decreased transepithelial electrical resistance, and individual enterocytes pulled apart. Enterotoxin pretreatment decreased internalization of L. monocytogenes (P < 0.01) but increased (P < 0.01) internalization of the other strains of enteric bacteria. Augmented bacterial internalization was associated with preferential bacterial adherence on the exposed lateral surface of enterotoxin-treated enterocytes.
Are malignant pleural effusion supernatants substitutes for metastatic pleural tumor tissues in EGFR mutation test in patients with advanced lung adenocarcinoma?	Though the possibility of using malignant pleural effusions (MPEs) as alternatives for metastatic pleural tumor tissues (MPTTs) in epidermal growth factor receptor (EGFR) mutation test has been examined, due to the lack of studies comparing the results in matching MPEs and MPTTs, the clinical value of MPEs for advanced adenocarcinoma patients with pleural effusions is not confirmed. EGFR mutation statuses in matching MPTTs, MPE supernatants and cell blocks, of 41 patients with advanced lung adenocarcinoma as diagnosed by thoracoscopy were analyzed using amplification refractory mutation system (ARMS). EGFR mutations were detected in 46.3% (19/41) of MPTTs, 43.9% (18/41) of MPE supernatants and 56.3% (18/32) of MPE cell blocks by ARMS analysis. Generally, the same EGFR statuses were identified in both MPTTs and matching MPE cell blocks of 81.3% patients (26/32), whereas MPTTs and matching MPE supernatants of 87.8% (36/41) patients shared the same EGFR status. Compared with EGFR mutation detection in MPTTs, the sensitivity of EGFR mutation detection in MPE-cell blocks was 87.5% (14/16), specificity was 75.0% (12/16), while the sensitivity of EGFR mutation detection in MPE-supernatants was 84.2% (16/19), specificity was 90.9% (20/22).	Recent research suggests that body vitamin D levels are decreased in coronary heart disease and diabetes, but it is unclear which cardiovascular risk factors are related to vitamin D status. To examine the relation between vitamin D status and major cardiovascular risk factors. Serum 25-hydroxyvitamin D3, a marker of recent sun exposure and vitamin D status, was measured in 390 New Zealand residents (95 Pacific Islanders, 74 Maori and 221 others mostly of European descent), who were part of a larger cross-sectional survey of a workforce (n = 5677) aged 40-64 years. Serum 25-hydroxyvitamin D3 levels were significantly lower in Pacific Islanders (mean (SE) = 56 (3) nmol/L; p = 0.0001) and Maoris (68 (3) nmol/L; p = 0.036) compared with Europeans (75 (2) nmol/L) after adjusting for age, sex and time of year. Also adjusting for ethnic group, 25-hydroxyvitamin D3 was higher in people doing vigorous (aerobic) leisure physical activities (71 (2) nmol/L; p = 0.0066) and moderate (non-aerobic) activities (68 (3) nmol/L; p = 0.12) compared with those who were inactive (63 (2) nmol/L). However, 25-hydroxyvitamin D3 was unrelated to body mass index, serum lipids, blood pressure or cigarette smoking.
Is cardioembolic stroke frequent in late recurrence after transient ischemic attack?	Transient ischemic attack (TIA) is often followed by a stroke episode. Differences between early and late recurrent stroke, however, have not been elucidated. We enrolled 133 consecutive patients with acute ischemic stroke who presented to our hospital and had previously been diagnosed with TIA. They were divided into 5 groups according to the interval between TIA and subsequent stroke: <48 hours (group 1); 48 hours to 1 week (group 2); 1 week to 1 month (group 3); 1 month to 3 months (group 4); and >3 months (group 5). Patients who underwent recurrent stroke within and after 1 week subsequent to TIA (the early and late recurrence groups, respectively) were compared with regard to clinical findings. Of the 133 patients, 46 (34.6%) were in group 1, 29 (21.8%) in group 2, 23 (17.3%) in group 3, 18 (13.5%) in group 4, and 17 (12.8%) in group 5. Most of the noncardioembolic strokes were observed shortly after TIA, while the percentage of cardioembolic stroke remained high even after long post-TIA periods. The prevalence of atrial fibrillation (AF) was higher in the late recurrence group than in the early recurrence group (41.4% v 24.0%, P = .033). Among 42 patients with AF, 12 (28.6%) were newly diagnosed at the time of stroke.	S100A4 has been shown to be increased in osteoarthritic (OA) cartilage and to stimulate chondrocytes to produce matrix metalloproteinase 13 (MMP-13) through activation of the receptor for advanced glycation end products (RAGE). The aim of this study was to examine the mechanism of S100A4 secretion by chondrocytes. Human articular chondrocytes isolated from ankle cartilage were stimulated with 10 ng/ml of interleukin-1beta (IL-1beta), IL-6, IL-7, or IL-8. Cells were pretreated with either a JAK-3 inhibitor, brefeldin A, or cycloheximide. Immunoblotting with phospho-specific antibodies was used to determine the activation of signaling proteins. Secretion of S100A4 was measured in conditioned media by immunoblotting, and MMP-13 was measured by enzyme-linked immunosorbent assay. Chondrocyte secretion of S100A4 was observed after treatment with IL-6 or IL-8 but was much greater in cultures treated with equal amounts of IL-7 and was not observed after treatment with IL-1beta. IL-7 activated the JAK/STAT pathway, with increased phosphorylation of JAK-3 and STAT-3, leading to increased production of S100A4 and MMP-13. Overexpression of a dominant-negative RAGE construct inhibited the IL-7-mediated production of MMP-13. Pretreatment of chondrocytes with a JAK-3 inhibitor or with cycloheximide blocked the IL-7-mediated secretion of S100A4, but pretreatment with brefeldin A did not.

Subsets and Splits

No community queries yet

The top public SQL queries from the community will appear here once available.