title stringlengths 0 1.13k | abstract stringlengths 1 15.7k | PMID int64 22 36.5M |
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Developmental coordination disorder in "apparently normal" schoolchildren born extremely preterm. | To determine the prevalence of developmental coordination disorder (DCD) in "apparently normal" extremely premature (<29 weeks) or extremely low birthweight (<1000 g) schoolchildren at 8 years of age and whether motor skill assessments at an earlier age could predict DCD. From a neonatal intensive care unit cohort, 50 of the 53 eligible children (IQ >84 and without disabilities at age 5 and residing in Sydney metropolitan) and full-term classroom controls matched for gender and age were assessed with the Movement Assessment Battery for Children (MABC) at school. Previous Griffith's Scales (1 and 3 years) and Peabody Motor Scales (3 and 5 years) results were evaluated for prediction. The prevalence of DCD (MABC impairment scores >1 SD below the norm) was significantly higher in the study group than controls (42% vs 8%, respectively), and severe DCD (scores >1.5 SD) was also significantly higher (30% vs 0%). DCD was independently associated with prolonged rupture of membranes and retinopathy of prematurity but not with parental education or occupation. Motor assessment using Peabody Fine Motor Scales at 3 years with a cut-off of <27th centile was the best predictor of DCD (areas under curve 78%). Apparently normal high-risk infants are at risk of motor dysfunction into their school years. Most of these could be identified at age 3. | 18,838,419 |
Saturation mutagenesis reveals that GLU54 of norovirus 3C-like protease is not essential for the proteolytic activity. | The norovirus 3C-like protease is a member of the chymotrypsin-like serine protease superfamily. Previous characterization of its crystal structure has implicated the Glu54-His30-Cys139 triad in the catalysis. In the present study, the Glu54 residue of the protease was subjected to site-saturation mutagenesis, with the result that nearly half of the mutants retained the significant proteolytic activity. It was suggested that a carboxylate at position 54 was not essential for the activity. The in vitro assays of the proteolysis revealed that most of Glu54 mutants retained relatively high proteolytic activity. When the Glu54 mutation was combined with the Ser mutation of the Cys139 residue, a nucleophile, only the Asp54 and Gln54 mutations showed proteolytic activity comparable to that of the Ser139 single mutant, suggesting that a hydrogen bond between Glu54 and His30 was critical in the Ser139 background. These results suggested that the mechanism of the proteolysis by the wild-type norovirus 3C-like protease was different from that of typical chymotrypsin-like serine proteases. | 18,838,436 |
Early individualised parenteral nutrition for preterm infants. | Considerable effort should be made to optimise parenteral nutrition of preterm infants in order to limit the development of postnatal growth restriction. A monocentric before-and-after study design was used to determine the effects of computerising parenteral nutrition ordering on the composition of parenteral nutrition (PN) solutions and early clinical outcomes of preterm infants born < or =28 weeks of gestation. Parenteral protein intake during the first week of life and parenteral lipid, glucose and energy intakes during the first and second week of life were significantly higher in infants assessed after the introduction of computerised parenteral nutrition ordering. This led to a significant reduction in the cumulative energy deficit over the first 28 days of life and to an improvement in both early growth and pulmonary outcome. Computerising the PN ordering process improves the nutrient content of the PN solutions and early postnatal outcome. | 18,838,470 |
Oesophageal and gastric intestinal-type adenocarcinomas show the same male predominance due to a 17 year delayed development in females. | Upper gastrointestinal adenocarcinomas show an unexplained male predominance that is more apparent in oesophagus than stomach and in intestinal than diffuse histological subtype. We have conducted a population-based study to determine whether the gender phenomenon is primarily related to the anatomical site or the histological subtype. Of 3270 gastric and oesophageal cancers recorded in the West of Scotland Cancer Registry, 1998-2002, 812 were randomly selected for detailed analysis. The Lauren histological subtype of adenocarcinoma was determined by reviewing 1204 original reports and 3241 biopsies. Analysis included 405 non-cardia cancers, 173 cardia cancers and 209 oesophageal adenocarcinomas. Crude incidence rate of intestinal subtype was higher in males (23.86/100,000 person-years) versus females (9.00/100,000 person-years), giving a male/female (M/F) ratio of 2.65 whereas diffuse subtype was similar for both genders (5.58 vs 5.20/100,000 person-years) yielding M/F of 1.07. The M/F ratios for oesophageal, cardia and non-cardia gastric cancer were 3.5, 2.0 and 1.6, respectively. Multiple logistic regression indicated that the odds of male gender was related to the histological subtype rather than anatomical location (odds ratio 2.6, 95% confidence interval 1.78 to 3.9). Curve fitting of the age-specific incidence of intestinal subtype indicated that similar functions describe the rise in incidence with age in males and in females. However, the age-specific incidence of female intestinal subtype was delayed by 17.3 years. The M/F ratio of intestinal subtype was 3.41 at age <50 years, peaked at 7.86 at age 50-59 years and then showed a progressive decrease after 50-60 years of age. Male predominance of upper gastrointestinal adenocarcinoma is related to the intestinal histological subtype rather than tumour location and is due to marked delayed development of this subtype in females prior to 50-60 years of age. | 18,838,486 |
Tolerance to the cataleptic effect that follows repeated nitric oxide synthase inhibition may be related to functional enzymatic recovery. | Systemic or intra-striatal acute administration of nitric oxide synthase (NOS) inhibitors causes catalepsy in rodents. This effect disappears after sub-chronic treatment. The aim of the present study was to investigate if this tolerance is related to changes in the expression of NOS or dopamine-2 (D2) receptor or to a recovery of NOS activity. Male albino Swiss mice (25-30 g) received single or sub-chronic (once a day for 4 days) i.p. injections of saline or L-nitro-arginine (L-NOARG, 40 mg/kg), a non-selective inhibitor of neuronal nitric oxide synthase (nNOS). Twenty-four hours after the last injection, the animals were killed and their brains were removed for immunohistochemistry assay to detect the presence of nNOS or for 'in-situ' hybridisation study using (35)S-labeled oligonucleotide probe complementary to D2 receptor mRNA. The results were analysed by computerised densitometry. Independent groups of animals received the same treatment, but were submitted to the catalepsy test and had their brain removed to measure nitrite and nitrate (NOx) concentrations in the striatum. Acute administration of L-NOARG caused catalepsy that disappeared after sub-chronic treatment. The levels of NOx were significantly reduced after acute L-NOARG treatment. The decrease in NOx after drug injection suffered a partial tolerance after sub-chronic treatment. The catalepsy time after acute or sub-chronic treatment with L-NOARG was negatively (r = -0.717) correlated with NOx levels. Animals that received repeated L-NOARG injections also showed an increase in the number of nNOS-positive neurons in the striatum. No change in D2 receptor mRNA expression was found in the dorsal striatum, nucleus accumbens and substantia nigra. Together, these results suggest that tolerance to L-NOARG cataleptic effects do not depend on changes in D2 receptors. They may depend, however, on plastic changes in nNOS neurons resulting in partial recovery of NO formation in the striatum. | 18,838,497 |
Expression and functional analysis of CYP2D6.24, CYP2D6.26, CYP2D6.27, and CYP2D7 isozymes. | The objectives of this study were to compare the drug-metabolizing activity of human CYP2D6.24 (I297L), CYP2D6.26 (I369T), and CYP2D6.27 (E410K) allelic isoforms with wild-type CYP2D6.1 and to express the CYP2D7 protein derived from an indel polymorphism (CYP2D7 138delT) and investigate its possible codeine O-demethylase activity. Successful creation of individual cDNAs corresponding to CYP2D6*24 (2853 A>C), CYP2D6*26 (3277 T>C), and CYP2D6*27 (3853 G>A) allelic variants and CYP2D7 was achieved via molecular cloning. The corresponding proteins, CYP2D6.24, CYP2D6.26, CYP2D6.27, and CYP2D7, were expressed in insect cells by using a baculovirus-mediated expression system. All CYP2D proteins showed the empirical carbon monoxide difference spectra. We were surprised to find that the CYP2D7 protein was detected mainly in mitochondrial fractions, whereas all CYP2D6 allelic isoforms were present in the microsomal fraction. Furthermore, CYP2D7 did not produce any morphine from codeine. In contrast, CYP2D6.24, CYP2D6.26, and CYP2D6.27 allelic isoforms all showed active drug-metabolizing activities toward both codeine and dextromethorphan O-demethylation. Whereas CYP2D6.24 exhibited the highest intrinsic clearance in dextromethorphan O-demethylation (approximately 6-fold higher than that by CYP2D6.1), it had the lowest enzyme efficiency in codeine O-demethylation (approximately 50% lower than that by CYP2D6.1). Overall, the enzymatic consequences of CYP2D6 allelic isozymes are substrate dependent. These data would help preclinical and clinical assessments of the metabolic elimination of drugs that are mediated by human CYP2D enzyme. | 18,838,503 |
Methionine-loading rapidly impairs endothelial function, by mechanisms independent of endothelin-1: evidence for an association of fasting total homocysteine with plasma endothelin-1 levels. | Homocysteinemia is associated with elevated oxidative stress and impaired endothelial function. In the present study we examined the impact of oxidative stress in the development of endothelial dysfunction in both chronic and acute (methionine-induced) homocysteinemia in humans. We also examined the role of endothelin-1 (ET-1) in the development of endothelial dysfunction in these two conditions. In this double-blind placebo controlled study, 28 subjects of both genders (14 with homocysteinemia and 14 healthy controls) underwent methionine-loading (100mg/Kg body weight) in a standard juice, containing vitamins C (2g) plus E (800IU) (n = 14) or no vitamins (placebo group, n = 14). Forearm vasodilatory response to reactive hyperemia, plasma total homocysteine (tHcy), oxidized LDL (ox-LDL), ET-1 and soluble vascular cell adhesion molecule (sVCAM-1), were evaluated at baseline and 4 hours post methionine loading (4hPML). Chronic homocysteinemia was associated with increased oxLDL (p < 0.01), higher ET-1 (p < 0.05) and impaired endothelial function (p < 0.01). However, oxLDL (but not ET-1) was increased 4hPML in the placebo group, an effect prevented by antioxidant vitamins. The development of severe endothelial dysfunction 4hPML was not however prevented by antioxidants. In linear regression analysis, fasting tHcy was an independent predictor of baseline oxLDL (p = 0.0001), but not of ET-1 levels. On the contrary, oxLDL was the main predictor of ET-1 (p = 0.008), suggesting that tHcy may increase ET-1 by enhancing the production of oxLDL. Both chronic and acute methionine-induced homocysteinemia are associated with elevated oxidative stress status. Although ET-1 is increased in chronic homocysteinemia, it does not participate in the rapid development of endothelial dysfunction after methionine loading. These findings suggest that despite its potential role in chronic homocysteinemia, ET-1 has a limited contribution to the development of endothelial dysfunction in acute, methionine-induced homocysteinemia in humans. | 18,838,525 |
Food consumption and the risk of type 1 diabetes in children and youth: a population-based, case-control study in Prince Edward Island, Canada. | The objective of this study was to determine if the consumption of certain foods during the year prior to diagnosis of type 1 diabetes mellitus (T1D) was associated with the risk of developing T1D in children and youth residing in Prince Edward Island, Canada. Cases (n = 57) consisted of newly diagnosed patients with T1D during 2001 to 2004. Controls (n = 105) were randomly selected from the province's population, and matched to cases by age at diagnosis and sex. Food consumption in cases and controls was assessed using two previously validated food frequency questionnaires, and a survey was developed to collect information on potential environmental and genetic risk factors. The median age at diagnosis was nine years, and 67% of cases were male. After controlling for the matched variables and four significant environmental and genetic risk factors (family members with T1D, the number of infections during the first two years of life, place of residence, and father's education) in the final logistic regression model, the consumption of regular soft drinks (OR = 2.78, 95% CI = 1.21, 6.36) and eggs (OR = 2.50, 95% CI = 1.09, 5.75) were significant risk factors of T1D, when consumed once per week or more often. Diet may play a role in the development of T1D. However, further research is needed to confirm these observed associations. | 18,838,530 |
Vitamin B6 is associated with depressive symptomatology in Massachusetts elders. | We examined the cross-sectional relationship between dietary vitamin B6 and plasma pyridoxyl-5'-phosphate concentrations (PLP) with depressive symptomatology among a representative sample of 618 elderly Caribbean Hispanics, and a neighborhood based comparison group of 251 non-Hispanic white (NHW) older adults in Massachusetts. Depressive symptomatology was assessed with the Center for Epidemiologic Studies Depression Scale (CES-D). 41% of Hispanics and 22.6% of NHWs had CES-D scores greater than 16, indicating depressive caseness. Dietary intake was calculated from a semi-quantitative food frequency questionnaire (FFQ) designed for this population. PLP was significantly associated with CES-D score and depressive caseness in the total sample and in non-supplement users. Deficient levels of plasma PLP (plasma PLP < 20 nmol/L) approximately doubled the likelihood of depressive caseness. Total intake (diet + supplement) of vitamin B(6) was not associated with these outcomes. However, dietary vitamin B(6) was significantly associated with CES-D score and depressive caseness. Longitudinal studies are needed to clarify the direction of causality between vitamin B6 and depressive symptoms. | 18,838,531 |
Glycogen synthase kinase 3beta-mediated serine phosphorylation of the human glucocorticoid receptor redirects gene expression profiles. | Aberrant glycogen synthase kinase 3beta (GSK-3beta) activity is associated with the progression of several pathological conditions such as diabetes, Alzheimer's, and cancer. GSK-3beta regulates cellular processes by directly phosphorylating metabolic enzymes and transcription factors. Here, we discovered a new target for GSK-3beta phosphorylation: the human glucocorticoid receptor (GR). Glucocorticoid signaling is essential for life and regulates diverse biological functions from cell growth to metabolism to apoptosis. Specifically, we found hormone-dependent GR phosphorylation on serine 404 by GSK-3beta. Cells expressing a GR that is incapable of GSK-3beta phosphorylation had a redirection of the global transcriptional response to hormone, including the activation of additional signaling pathways, in part due to the altered ability of unphosphorylatable GR to recruit transcriptional cofactors CBP/p300 and the p65 (RelA) subunit of NF-kappaB. Furthermore, GSK-3beta-mediated GR phosphorylation inhibited glucocorticoid-dependent NF-kappaB transrepression and attenuated the glucocorticoid-dependent cell death of osteoblasts. Collectively, our results describe a novel convergence point of the GSK-3beta and the GR pathways, resulting in altered hormone-regulated signaling. Our results also provide a mechanism by which GSK-3beta activity can dictate how cells will ultimately respond to glucocorticoids. | 18,838,540 |
The keratin-binding protein Albatross regulates polarization of epithelial cells. | The keratin intermediate filament network is abundant in epithelial cells, but its function in the establishment and maintenance of cell polarity is unclear. Here, we show that Albatross complexes with Par3 to regulate formation of the apical junctional complex (AJC) and maintain lateral membrane identity. In nonpolarized epithelial cells, Albatross localizes with keratin filaments, whereas in polarized epithelial cells, Albatross is primarily localized in the vicinity of the AJC. Knockdown of Albatross in polarized cells causes a disappearance of key components of the AJC at cell-cell borders and keratin filament reorganization. Lateral proteins E-cadherin and desmoglein 2 were mislocalized even on the apical side. Although Albatross promotes localization of Par3 to the AJC, Par3 and ezrin are still retained at the apical surface in Albatross knockdown cells, which retain intact microvilli. Analysis of keratin-deficient epithelial cells revealed that keratins are required to stabilize the Albatross protein, thus promoting the formation of AJC. We propose that keratins and the keratin-binding protein Albatross are important for epithelial cell polarization. | 18,838,552 |
The test validation summary. | Common rates employed in classificatory testing are the true positive rate (TPR), false positive rate (FPR), positive predictive power (PPP), and negative predictive power (NPP). FPR and TPR are estimated from research samples representing populations to be distinguished by classificatory testing. PPP and NPP are used by clinicians to classify test takers into populations. PPP and NPP depend on the base rate (BR) of population members in the clinician's sample. The authors introduce the test validation summary (TVS) as a means to report within a single graph the FPR and TPR and the ranges of PPP and NPP across all potential sample BRs for any chosen cut score. The authors investigate how the TVS has other applications, including the estimation of local BR for the condition of interest and the estimation of standard errors for FPR and TPR when estimated across multiple independent validation studies of the classificatory test. | 18,838,580 |
Development of an optimized dose for coformulation of zidovudine with drugs that select for the K65R mutation using a population pharmacokinetic and enzyme kinetic simulation model. | In vitro selection studies and data from large genotype databases from clinical studies have demonstrated that tenofovir disoproxil fumarate and abacavir sulfate select for the K65R mutation in the human immunodeficiency virus type 1 polymerase region. Furthermore, other novel non-thymine nucleoside reverse transcriptase (RT) inhibitors also select for this mutation in vitro. Studies performed in vitro and in humans suggest that viruses containing the K65R mutation remained susceptible to zidovudine (ZDV) and other thymine nucleoside antiretroviral agents. Therefore, ZDV could be coformulated with these agents as a "resistance repellent" agent for the K65R mutation. The approved ZDV oral dose is 300 mg twice a day (b.i.d.) and is commonly associated with bone marrow toxicity thought to be secondary to ZDV-5'-monophosphate (ZDV-MP) accumulation. A simulation study was performed in silico to optimize the ZDV dose for b.i.d. administration with K65R-selecting antiretroviral agents in virtual subjects using the population pharmacokinetic and cellular enzyme kinetic parameters of ZDV. These simulations predicted that a reduction in the ZDV dose from 300 to 200 mg b.i.d. should produce similar amounts of ZDV-5'-triphosphate (ZDV-TP) associated with antiviral efficacy (>97% overlap) and reduced plasma ZDV and cellular amounts of ZDV-MP associated with toxicity. The simulations also predicted reduced peak and trough amounts of cellular ZDV-TP after treatment with 600 mg ZDV once a day (q.d.) rather than 300 or 200 mg ZDV b.i.d., indicating that q.d. dosing with ZDV should be avoided. These in silico predictions suggest that 200 mg ZDV b.i.d. is an efficacious and safe dose that could delay the emergence of the K65R mutation. | 18,838,591 |
Cost and cost-effectiveness of the COMBINE study in alcohol-dependent patients. | The COMBINE (Combined Pharmacotherapies and Behavioral Intervention) clinical trial recently evaluated the efficacy of medications, behavioral therapies, and their combinations for the outpatient treatment of alcohol dependence. The costs and cost-effectiveness of these combinations are unknown and of interest to clinicians and policy makers. To evaluate the costs and cost-effectiveness of the COMBINE Study interventions after 16 weeks of treatment. A prospective cost and cost-effectiveness study of a randomized controlled clinical trial. Eleven US clinical sites. One thousand three hundred eighty-three patients having a diagnosis of primary alcohol dependence. The study included 9 treatment groups; 4 groups received medical management for 16 weeks with naltrexone, 100 mg/d, acamprosate, 3 g/d, or both, and/or placebo; 4 groups received the same therapy as mentioned earlier with combined behavioral intervention; and 1 group received combined behavioral intervention only. Incremental cost per percentage point increase in percentage of days abstinent, incremental cost per patient of avoiding heavy drinking, and incremental cost per patient of achieving a good clinical outcome. On the basis of the mean values of cost and effectiveness, 3 interventions are cost-effective options relative to the other interventions for all 3 outcomes: medical management (MM) with placebo ($409 per patient), MM plus naltrexone therapy ($671 per patient), and MM plus combined naltrexone and acamprosate therapy ($1003 per patient). To our knowledge, this is only the second prospective cost-effectiveness study with a randomized controlled clinical trial design that has been performed for the treatment of alcohol dependence. Focusing only on effectiveness, MM-naltrexone-acamprosate therapy is not significantly better than MM-naltrexone therapy. However, considering cost and cost-effectiveness, MM-naltrexone-acamprosate therapy may be a better choice, depending on whether the cost of the incremental increase in effectiveness is justified by the decision maker. | 18,838,638 |
Missed diagnosis of critical congenital heart disease. | To evaluate the rate and the clinical and demographic characteristics of missed diagnosis of critical congenital heart disease (CCHD). Population-based retrospective study of 1989-2004 California statewide death registry data. California. The study cohort consisted of 898 infants who died of CCHD at 1 to 364 days of age who either did not undergo surgery or had an unknown surgery status. From all patients who met these initial criteria, we examined (1) whether autopsies were performed and autopsy results were used to establish the cause of death, (2) whether autopsies were performed but the results were not used to establish a cause of death, and (3) whether infants with hypoplastic left heart syndrome (HLHS) were potentially receiving comfort care. Missed and possibly late diagnosis of CCHD. Among 152 infants with a missed CCHD diagnosis, the median age at death was 13.5 days. More than 50% of patients with a missed CCHD diagnosis (n = 78) died at home or in the hospital emergency department. The most common diagnoses were HLHS and coarctation of aorta. There were an average of 10 patients with missed CCHD diagnoses and 20 patients with late diagnoses in California per year. The total annual number of patients with missed or late diagnoses decreased in 1989-1999 and remained unchanged in 2000-2004. Up to 30 infants per year died of a missed or possibly late diagnosis of CCHD in California. Most deaths due to a missed diagnosis were from HLHS and coarctation of the aorta. Because the median age at death was younger than 2 weeks, a careful cardiovascular evaluation for left heart obstructive CHD should be performed during the first postdischarge visit to a pediatrician's office at 3 to 5 days of age. | 18,838,650 |
Noninvasive diagnosis of fetal aneuploidy by shotgun sequencing DNA from maternal blood. | We directly sequenced cell-free DNA with high-throughput shotgun sequencing technology from plasma of pregnant women, obtaining, on average, 5 million sequence tags per patient sample. This enabled us to measure the over- and underrepresentation of chromosomes from an aneuploid fetus. The sequencing approach is polymorphism-independent and therefore universally applicable for the noninvasive detection of fetal aneuploidy. Using this method, we successfully identified all nine cases of trisomy 21 (Down syndrome), two cases of trisomy 18 (Edward syndrome), and one case of trisomy 13 (Patau syndrome) in a cohort of 18 normal and aneuploid pregnancies; trisomy was detected at gestational ages as early as the 14th week. Direct sequencing also allowed us to study the characteristics of cell-free plasma DNA, and we found evidence that this DNA is enriched for sequences from nucleosomes. | 18,838,674 |
Structural insights from a P450 Carrier Protein complex reveal how specificity is achieved in the P450(BioI) ACP complex. | Cytochrome P450(BioI) (CYP107H1) from the biotin operon of Bacillus subtilis forms a seven-carbon diacid through a multistep oxidative cleavage of a fatty acid linked to acyl carrier protein (ACP). Crystal structures of P450(BioI) in complex with three different length fatty acyl-ACP (Escherichia coli) ligands show that P450(BioI) binds the fatty acid such as to force the carbon chain into a U-shape above the active site heme. This positions the C7 and C8 carbons for oxidation, with a large additional cavity extending beyond the heme to accommodate the methyl termini of fatty acids beyond the site of cleavage. The structures explain the experimentally observed lack of stereo- and regiospecificity in the hydroxylation and cleavage of free fatty acids. The P450(BioI)-ACP complexes represent the only structurally characterized P450-carrier protein complexes to date, which has allowed the generation of a model of the interaction of the vancomycin biosynthetic P450 OxyB with its proposed carrier protein bound substrate. | 18,838,690 |
Aptamer-based endocytosis of a lysosomal enzyme. | Enzyme replacement therapy for lysosomal storage diseases is currently based on endocytosis of lysosomal enzymes via the mannose or mannose 6-phosphate receptors. We are developing a technology for endocytosis of lysosomal enzymes that depends on generic, chemically conjugated reagents. These reagents are aptamers (single-stranded nucleic acid molecules) selected to bind to the extracellular domain of the mouse transferrin receptor. After selection, an RNA aptamer and a DNA aptamer were modified with biotin and linked to dye-labeled streptavidin for detection by confocal microscopy. Aptamer-streptavidin conjugates showed saturable uptake into mouse fibroblasts (Ltk(-) cells), which could be inhibited by an excess of free aptamer but not by tRNA, calf thymus DNA, or transferrin. The RNA aptamer-streptavidin conjugate was mouse-specific, as human cells (293T) did not take it up unless first transfected with the mouse transferrin receptor. Some streptavidin separated from the recycling pathway of transferrin and colocalized with lysosomes. After characterization in the model system, the DNA aptamer was conjugated to a lysosomal enzyme, alpha-l-iduronidase, from which mannose 6-phosphate had been removed. The aptamer had been modified by attachment of terminal glycerol for oxidation by periodate and reaction of the resulting aldehyde with amino groups on the protein. Dephospho-alpha-L-iduronidase-aptamer conjugate was taken up in saturable manner by alpha-L-iduronidase-deficient mouse fibroblasts, with half-maximal uptake estimated as 1.6 nM. Endocytosed enzyme-aptamer conjugate corrected glycosaminoglycan accumulation, indicating that it reached lysosomes and was functional in those organelles. Both uptake and correction were inhibited by unconjugated aptamer, confirming the role of the aptamer in receptor-mediated endocytosis. | 18,838,694 |
Clinical manifestations and antiretroviral management of HIV/AIDS patients with tuberculosis co-infection in Kramat 128 Hospital. | to give a description of HIV-AIDS and tuberculosis co-infection in Jakarta, viewed from the perspective of virologic and immunologic status and the correct selection of antiretrovirals. cross-sectional descriptive study was performed on the outpatient clinic of Kramat 128, from June to July 2007. Tuberculosis infection was confirmed chest X-ray or sputum acid fast smear. Viral load was determined by Polymerase Chain Reaction (PCR) and CD4 count done by flow cytometry. The data were then analyzed using SPSS 14th and Chi Square tests for proportional data. the study enrolled 130 patients with the prevalence of tuberculosis co-infection of 66.9% (n=87). The TB co-infected patients came with more clinical manifestations (3-4 manifestations) than the non co-infected ones (2-3 manifestations; p<0.001). They also underwent more hospitalizations (44.8% vs. 11.6%, p=0.003), had lower CD4 levels (126.49 cell/microL vs. 240.68 cell/microL; p=0.001) and more patients with CD4 levels of below 100 cell/microL (64.6% vs. 25.6%; p<0.001). The co-infected patients had more virologic failure than the non co-infected ones (38% vs. 12.5%; p=0.030), and so did the co-infected patients treated with nevirapine than those treated with efavirenz (37.8% vs. 6.3%; p=0.019). tuberculosis co-infection complicated the clinical management of People Living with HIV-AIDS (PLWHA) and the antiretroviral regimen selection in these patients need to be modified. Subsequent studies were needed to confirm this study result of superior efavirenz based therapy in the TB co-infected PLWHA. | 18,838,749 |
The new three-dimensional supramolecule bis{mu-2-[(4-hydroxybenzoyl)hydrazonomethyl]phenolato}bis[aquacopper(II)] dinitrate. | In the title centrosymmetric binuclear complex, [Cu(2)(C(14)H(11)N(2)O(3))(2)(H(2)O)(2)](NO(3))(2), the two metal centres are bridged by the phenolate O atoms of the ligand, forming a Cu(2)O(2) quadrangle. Each Cu atom has a distorted square-pyramidal geometry, with the basal donor atoms coming from the O,N,O'-tridentate ligand and a symmetry-related phenolate O atom. The more weakly bound apical donor O atom is supplied by a coordinated water molecule. When a further weak Cu...O interaction with the 4-hydroxy O atom of a neighbouring cation is considered, the extended coordination sphere of the Cu atom can be described as distorted octahedral. This interaction leads to two-dimensional layers, which extend parallel to the (100) direction. The two-dimensional polymeric structure contrasts with other reported structures involving salicylaldehyde benzoylhydrazone ligands, which are usually discrete mono- or dinuclear Cu complexes. The nitrate anions are involved in a three-dimensional hydrogen-bonding network, featuring intermolecular N-H...O and O-H...O hydrogen bonds. | 18,838,761 |
Electrophysiological properties of NtTPK1 expressed in yeast tonoplast. | The patch clamp technique using enlarged yeast tonoplasts is an effective approach to characterizing the Nicotiana tabacum plant tonoplast K+ channel, NtTPK1. We report here that the NtTPK1-mediated currents comprise two phase components, both which were found to be highly selective for K+ over Na+ and Cl-. | 18,838,784 |
Improved solubilization of recombinant human growth hormone inclusion body produced in Escherichia coli. | Recombinant human growth hormone (r-hGH) overexpressed in Escherichia coli forms inactive and insoluble aggregates as inclusion bodies in the cytoplasm. The efficient solubilization of inclusion bodies is critical for cost-effective production. Contrary to a previous report, in our production system, the solubilization method by alkaline treatment including 2 M urea was ineffective. Hence various buffers containing different concentrations of urea or guanidine hydrochloride (GnHCl) at neutral and alkaline pH were attempted. Efficient solubilization (about 90%) was observed in 100 mM Tris buffer, pH 8.0, with more than 4 M GnHCl, and at pH 12.5 with more than 2 M GnHCl, but not with about 8 M of urea. The r-hGH solubilized at pH 12.5 containing 2 M GnHCl was refolded by simple dilution and purified by DEAE Sepharose anion-exchange chromatography. The biological activity of the resulting r-hGH was comparable with commercially available r-hGH in in vitro cell proliferation assay using the hGH-dependent cell line. | 18,838,803 |
Exploring the biosynthesis of natural products and their inherent suitability for the rational design of desirable compounds through genetic engineering. | Much effort has been invested in studying how natural products are biosynthesized, and great advances have been made in understanding how these compounds acquire their structural complexity and biological activities. In recent years, significant progress has been made due to the devoted efforts of scientists in this field and to technological advancements. Numerous details, applications, and innovative findings have been elucidated by scientists using biochemical, genetic, and molecular biological approaches. Here I present a comprehensive overview of highly valued biosynthetic proteins, polyketide synthase and nonribosomal peptide synthetase. I begin with "Diels-Alderase" a captivating enzyme that has the ability to catalyze a Diels-Alder reaction valued by chemists for its usefulness in chemical synthesis. A handful of these enzymes have been characterized and chemically authenticated. The most well understood enzyme of this category is macrophomate synthase. Secondly, I focus on the polyketide and nonribosomal peptide biosynthetic pathways and the enzyme assembly for producing its metabolite. Many important natural products are produced by this biosynthetic pathway as secondary metabolites, such as erythromycin, rifamycin, and FK520, as antibiotics and an immunosuppressive, respectively. I conclude with a discussion of nonribosomal peptides and their mechanistic pathways. Special attention will be devoted to de novo production of echinomycin in a heterologous manner, the earliest example of totally engineered biosynthesis of the biologically active form of a nonribosomal peptide host in Escherichia coli. | 18,838,806 |
Depigmenting mechanisms of all-trans retinoic acid and retinol on B16 melanoma cells. | We assessed the effects of ATRA and retinol on melanogenesis in murine B16 melanoma cells. In the present study, ATRA and retinol inhibited melanin synthesis in melanoma cells stimulated by alpha-melanocyte stimulating hormone (alpha-MSH) or 3-isobutyl-1-methylxanthine (IBMX). To elucidate the target points of ATRA and retinol on melanogenesis, we performed western blotting for melanogenic proteins, such as tyrosinase, tyrosinase-related protein (TRP)-1, and TRP-2. ATRA inhibited the expression of tyrosinase and TRP-1, and retinol inhibited the expression of tyrosinase, in a dose-dependent manner. Neither ATRA nor retinol inhibited TRP-2 expression. There were no differences in melanogenic protein expression between the two stimulants tested, alpha-MSH and IBMX. Therefore, the depigmenting effect of ATRA and retinol might be due to inhibition of the signaling pathway between cAMP and tyrosinase transcription bound to tyrosinase expression. These results indicate that ATRA and retinol are candidate anti-melanogenic agents that they might be effective in hyperpigmentation disorders. | 18,838,813 |
Absorption, migration and kinetics in peripheral blood of orally administered ovalbumin in a mouse model. | Intestinal absorption of food proteins is well known, whereas its physiological significance remains to be investigated. Various amounts (1, 10 and 50 mg) of ovalbumin were orally administered to mice and the blood kinetics were subsequently analyzed by two-site ELISA. The blood ovalbumin concentration consistently reached its maximum (7-90 ng/ml) about 20 min after the oral administration and then gradually decreased in a dose-dependent manner. Only intact (45 kDa) and truncated (40 kDa) ovalbumins were always detected in the blood independently of the administration site, intra-stomach or intra-intestine, while various fragments of the protein were observed in the gastrointestinal lumen after the oral administration. Recognition by a specific monoclonal antibody and an acidic shift of its pI value suggested that the 40-kDa truncated ovalbumin was produced by intracellular limited proteolysis at its C-terminus. Such stable absorption and blood kinetics of undigested ovalbumin in normal mice suggest some sort of physiological significance for the intestinal uptake of intact food proteins. | 18,838,817 |
The metabolism and distribution of docosapentaenoic acid (n-6) in the liver and testis of growing rats. | To investigate the metabolism and distribution of docosapentaenoic acid (22:5n-6, DPA) in the liver and testis of growing rats, 22:5n-6 was administered to their dams. Newborn rats with a low hepatic arachidonic acid (20:4n-6, AA) level were generated by administrating a diet rich in docosahexaenoic acid (22:6n-3, DHA) but n-6 fatty acid (FA) free to pregnant dams. After parturition, 22:5n-6 or linoleic acid (18:2n-6, LA) was administered with a high level of 22:6n-3 to the dams until weaning. At weaning, the hepatic 20:4n-6 level was significantly highest in the DPA-DHA but not LA-DHA diet-fed animals. The hepatic delta-6 desaturase (D6D) mRNA abundance was significantly lower in both the LA-DHA and DPA-DHA diet-fed animals, connoted with the 20:4n-6 content recovered by 22:5n-6 that did not involve D6D and supporting the occurrence of retroconversion in the liver of the growing rats. The low D6D level in the 3-week-old testis was not in proportion to the elevated 22:5n-6 level, implying that early testicular 22:5n-6 accumulation might require supply from the circulation system. | 18,838,818 |
Preventive effect of Streptococcus thermophilus YIT 2001 on dextran sulfate sodium-induced colitis in mice. | We investigated the preventive effect of Streptococcus thermophilus YIT 2001, a lactic acid bacterum having high antioxidative activity, on acute colitis induced by 2.5% dextran sulfate sodium in mice, and compared the effect with that of S. thermophilus YIT 2084 which has lower antioxidative activity. Feeding S. thermophilus YIT 2001 decreased the disease activity index and level of lipid peroxide (the thiobarbituric acid reactive substance content) in the colonic mucosa. The hematocrit and hemoglobin concentrations in the blood of S. thermophilus YIT 2001-fed mice were higher than those of the control mice. S. thermophilus YIT 2084 had no significant effect on these parameters. The results suggest that the antioxidative activity of S. thermophilus YIT 2001 was involved in the improving effect on colitis. | 18,838,819 |
Improvement of L-lysine production by Methylophilus methylotrophus from methanol via the Entner-Doudoroff pathway, originating in Escherichia coli. | To improve the amino acid production by metabolic engineering, eliminating the pathway bottleneck is known to be very effective. The metabolic response of Methylophilus methylotrophus upon the addition of glucose and of pyruvate was investigated in batch cultivation. We found that the supply of pyruvate is a bottleneck in L-lysine production in M. methylotrophus from methanol as carbon source. M. methylotrophus has a ribulose monophosphate (RuMP) pathway for methanol assimilation, and consequently synthesized fructose-6-phosphate is metabolized to pyruvate via the Entner-Doudoroff (ED) pathway, and the ED pathway is thought to be the main pathway for pyruvate supply. An L-lysine producer of M. methylotrophus with an enhanced ED pathway was constructed by the introduction of the E. coli edd-eda operon encoding the enzyme involving the ED pathway. In this strain, the overall enzymatic activity of ED pathway, which is estimated by measuring the activities of 6-phosphogluconate dehydrogenase plus 2-keto-3-deoxy-6-phosphogluconate aldolase, was about 20 times higher than in the parent. This strain produced 1.2 times more L-lysine than the parent producer. Perhaps, then, the supply of pyruvate was a bottleneck in L-lysine production in the L-lysine producer of M. methylotrophus. | 18,838,820 |
Biological activities of Korean Citrus obovoides and Citrus natsudaidai essential oils against acne-inducing bacteria. | This study was designed to analyze the chemical composition of Citrus obovoides (Geumgamja) and Citrus natsudaidai (Cheonyahagyul) oils and to test their biological activities. These citrus essential oils were obtained by steam distillation of fruits collected from Jeju Island, Korea, and were analyzed using gas chromatograph (GC)-flame ionization detectors (FID) and GC-MS. Limonene and gamma-terpinene were the major components of the two citrus species. To evaluate in vitro anti-acne activity, they were tested against Propionibacterium acnes and Staphylococcus epidermidis, which are involved in acne. The Geumgamja and Cheonyahagyul oils exhibited antibacterial activity against both P. acnes and S. epidermidis. Their effects on DPPH radical scavenging, superoxide anion radical scavenging, and nitric oxide radical were also assessed. Cheonyahagyul and Geumgamja exhibited only superoxide anion radical-scavenging activity. To assess their potential usefulness in future cosmetic product applications, the cytotoxic effects of the two oils were determined by colorimetric MTT assays using two animal cell lines: normal human fibroblasts and HaCaT cells. They exhibited low cytotoxicity at 0.1 microl/ml in both cell lines. In addition, they reduced P. acnes-induced secretion of interleukin-8 (IL-8) and tumor necrosis factor alpha (TNF-alpha) in THP-1 cells, an indication of anti-inflammatory effects. Therefore, based on these results, we suggest that Geumgamja and Cheonyahagyul essential oils are attractive acne-mitigating candidates for topical application. | 18,838,824 |
Chemical composition and anti-inflammatory effects of essential oil from Farfugium japonicum flower. | In this study, the chemical composition and anti-inflammatory activities of hydrodistilled essential oil from Farfugium japonicum were investigated for the first time. The chemical constituents of the essential oil were further analyzed by GC-MS and included 1-undecene (22.43%), 1-nonene (19.83%), beta-caryophyllene (12.26%), alpha-copaene (3.70%), gamma-curcumene (2.86%), germacrene D (2.69%), and 1-decene (2.08%). The effects of the essential oil on nitric oxide (NO) and prostaglandin E2 (PGE(2)) production in lipopolysaccharide (LPS)-activated RAW 264.7 macrophages were also examined. The results indicate that the F. japonicum essential oil is an effective inhibitor of LPS-induced NO and PGE(2) production in RAW 264.7 cells. These inhibitory effects of the F. japonicum essential oil were accompanied by dose-dependent decreases in the iNOS and COX-2 mRNA expression. In order to determine whether F. japonicum essential oil can safely be applied to human skin, the cytotoxic effects of F. japonicum essential oil were determined by colorimetric MTT assays in human dermal fibroblast and keratinocyte HaCaT cells. F. japonicum essential oil exhibited low cytotoxicity at 100 mug/mL. Based on these results, we suggest that F. japonicum essential oil may be considered a potential anti-inflammatory candidate for topical application. | 18,838,835 |
Accuracy of spring-levered and piezo-electric pedometers in primary school Japanese children. | Pedometers are used in many studies because physical activities can be simply assessed using them. In addition to the spring-levered type, piezo-electric pedometers have recently been used. However, their accuracy in children has not been investigated in previous studies. In this study, we investigated the accuracy of spring-levered pedometer and piezo-electric pedometer step counts in comparison with hand-tallied step counts with children during self-paced walking. First to 6th-grade primary school children (394 subjects; 201 boys and 193 girls) walked with pedometers on an outdoor 50-m course, and the measured values were compared with actual steps at 3 speeds: normal, slow, and fast paces. The counts obtained by the spring-levered pedometer were significantly lower than the actual steps in most grades at all walking paces. In the normal- and fast-pace walking, the counts by spring-levered pedometer were significantly lower than the actual steps in all grades excluding the 5th grade. Moreover, the spring-levered pedometer underestimated by 25% or more in all grades at slow pace. In contrast, the percent error of the counts by the piezo-electric pedometers at normal pace were mostly within +/-3%, confirming their high accuracy. Based on these findings, spring-levered pedometers are not appropriate for children, whereas piezo-electric pedometers are useful for investigation of the physical activity of children. | 18,838,838 |
Ankle MRI for anterolateral soft tissue impingement: increased accuracy with the use of contrast-enhanced fat-suppressed 3D-FSPGR MRI. | To validate the use of contrast-enhanced (CE) fat-suppressed three-dimensional (3D) fast gradient-recalled acquisition in the steady state with radiofrequency spoiling (FSPGR) magnetic resonance imaging (MRI) for the diagnosis of anterolateral soft tissue impingement of the ankle, as compared to the use of routine ankle MRI. Contrast-enhanced fat-suppressed 3D-FSPGR MRI and routine MRI scans were retrospectively reviewed for 45 patients with arthroscopically proven anterolateral impingement. In addition, scans were reviewed in 45 control subjects with diagnoses other than impingement. Two radiologists independently reviewed the two sets of images in random order. Using areas (Az) under the receiver operating characteristic curve (ROC), we compared the depiction of anterolateral soft tissue impingement in the two sets of images. The overall accuracy for lesion characterization was significantly higher (p < 0.05) using the CE fat-suppressed 3D-FSPGR MR images (Az = 0.892 and 0.881 for reader 1 and 2, respectively) than using the routine MR images (Az = 0.763 and 0.745). The use of CE fat-suppressed 3D-FSPGR MRI enhanced impingement depiction in most cases. However, in cases with a thickened non-enhancing scar or joint effusion, the routine images better depicted a soft tissue mass that intruded into anterolateral gutter than the CE images. The use of CE fat-suppressed 3D-FSPGR MRI of the ankle allows a more accurate assessment of anterolateral soft tissue impingement of the ankle, as compared to the use of routine MRI. | 18,838,849 |
CT images of a malignant-transformed ovarian mature cystic teratoma with rupture: a case report. | A malignant transformation or a tumor rupture is a rare complication of ovarian mature cystic teratoma (MCT). A tumor rupture in a malignant-transformed MCT has never been reported in the literature. We present the CT images of a 39-year-old woman showing a large, predominantly cystic mass in the lower abdomen, with fat-fluid-level ascites. A contrast-enhanced solid component, with regional discontinuity within the cystic lesion, is also demonstrated. The pathologic diagnosis of the ruptured MCT unveils the malignant transformation (squamous cell carcinoma) and mesenteric carcinomatosis. | 18,838,856 |
Microarray and pathway analysis reveals decreased CDC25A and increased CDC42 associated with slow growth of BCL2 overexpressing immortalized breast cell line. | Bcl-2 is an anti-apoptotic protein that is frequently overexpressed in cancer cells but its role in carcinogenesis is not clear. We are interested in how Bcl-2 expression affects non-cancerous breast cells and its role in the cell cycle. We prepared an MCF10A breast epithelial cell line that stably overexpressed Bcl-2. We analyzed the cells by flow cytometry after synchronization, and used cDNA microarrays with quantitative reverse-transcription PCR (qRT-PCR) to determine differences in gene expression. The microarray data was subjected to two pathway analysis tools, parametric analysis of gene set enrichment (PAGE) and ingenuity pathway analysis (IPA), and western analysis was carried out to determine the correlation between mRNA and protein levels. The MCF10A/Bcl-2 cells exhibited a slow-growth phenotype compared to control MCF10A/Neo cells that we attributed to a slowing of the G(1)-S cell cycle transition. A total of 363 genes were differentially expressed by at least two-fold, 307 upregulated and 56 downregulated. PAGE identified 22 significantly changed gene sets. The highest ranked network of genes identified by IPA contained 24 genes. Genes that were chosen for further analysis were confirmed by qRT-PCR, however, the western analysis did not always confirm differential expression of the proteins. Downregulation of the phosphatase CDC25A could solely be responsible for the slow growth phenotype in MCF10A/Bcl-2 cells. Increased levels of GTPase Cdc42 could be adding to this effect. PAGE and IPA are valuable tools for microarray analysis, but protein expression results do not always follow mRNA expression results. | 18,838,868 |
Basics of particle therapy: introduction to hadrons. | With the arrival of 3-dimensional conformal radiation therapy and intensity modulated radiation therapy, radiation dose distributions in radiation oncology have improved dramatically over the past couple of decades. As part of a natural progression there recently has been a resurgence of interest in hadron therapy, specifically charged particle therapy, because of the even better dose distributions potentially achievable. In principle, using charged particle beams, radiation dose distributions can be achieved that surpass those possible with even the most sophisticated photon radiation delivery techniques. Certain charged particle beams might possess some biologic advantages in terms of tumor kill potential as well as this dosimetric advantage. The particles under consideration for such clinical applications all belong to the category of particles known as hadrons. This review introduces some of the elementary physics of the various hadron species previously used, currently used or being considered for future use in radiation oncology. | 18,838,888 |
Guiding the clinical nurse through research publication development. | Clinical nurses conduct research as a component of their professional role. The final step of the research process is communicating findings to the nursing community. Some staff nurses may be reluctant to assume the role of first-time author because of a lack of understanding of the basic mechanics of manuscript development. The nurse in staff development plays a vital role in guiding a novice author through the process. This article provides a guideline to assist the staff development educator when mentoring clinical nurses in this endeavor. | 18,838,901 |
Community nurses who thrive: the critical role of job engagement in the face of adversity. | Among community health nurses who thrive despite difficult working circumstances, habitual introspection and reflection about job engagement helped them make positive, adaptive adjustments in their working life. A practical implication is the need to educate nurses about the importance of reflection not only over nursing practice but also of habitual introspection and reflection about their job engagement. Nurses in staff development should teach and reinforce the needed skills and habits. | 18,838,896 |
Podoplanin (D2-40) is a highly effective marker of follicular dendritic cells. | The monoclonal antibody D2-40 recognizes the membrane protein podoplanin, which is an established marker for germ cell tumors, mesotheliomas, and other tumor types and is also expressed in a variety of normal cells including follicular dendritic cells (FDCs). To determine whether podoplanin represents an effective FDC marker for pathologic lymph nodes, we compared immunohistochemical studies (sensitivity, staining patterns, and intensity of staining) for podoplanin (D2-40) with those of the traditional FDC markers CD21, CD35, and clusterin. Paraffin sections of 26 lymph nodes were analyzed, including 4 cases of nodular lymphocyte-predominant Hodgkin lymphoma, 4 angioimmunoblastic T-cell lymphoma, 8 follicular lymphoma (including 3 cases with a component of diffuse large B-cell lymphoma), 5 hyaline-vascular Castleman disease, and 5 reactive lymph nodes with follicular hyperplasia. In all cases, qualitatively and quantitatively podoplanin represented a highly effective marker for detection of FDCs, with staining intensity equal to or greater than that observed for other FDC markers. This study demonstrates that podoplanin is an excellent marker for FDCs and adds to its growing list of diagnostic applications. | 18,838,918 |
The use of isotonic fluid as maintenance therapy prevents iatrogenic hyponatremia in pediatrics: a randomized, controlled open study. | Hypotonic fluids are widely used in pediatrics. Several articles have reported the risk of iatrogenic hyponatremia secondary to this practice. We primarily intend to determine whether the use of isotonic fluids prevents hyponatremia and, secondly, whether these fluids increase the incidence of adverse events. One hundred twenty-two pediatric patients hospitalized in intensive care unit requiring maintenance fluid therapy were randomized to receive isotonic fluids (isotonic group, NaCl = 140 mEq/L) or hypotonic fluids (hypotonic group, NaCl <100 mEq/L). Electrolyte blood concentration, glycaemia, and blood pressure were measured at 0, 6, and 24 hrs after the beginning of fluid therapy. Plasma creatinine, urine specific gravity, and urine electrolyte concentration were measured at 6 hrs. Standard intention-to-treat analysis and Bayesian analysis were conducted to assess the probability of hyponatremia and hypernatremia in each group. At the time of admission to hospital, no differences in natremia or the percentage of hyponatremia were found between groups. At 24 hrs, the percentage of hyponatremia in the hypotonic group was 20.6% as opposed to 5.1% in the isotonic group (p = 0.02). No differences in the number of adverse events other than hyponatremia were observed between groups. The use of hypotonic fluids increases the risk of hyponatremia when compared with isotonic fluids at 24 hrs following infusion (number needed to harm [confidence interval 95%] = 7[4;25]). In our sample, the use of isotonic fluids did not increase the incidence of adverse events compared with hypotonic fluids. | 18,838,929 |
Gas exchange and lung mechanics during high frequency ventilation in the perflubron-treated lung. | To identify the effect of perflubron on gas exchange and lung mechanics during high frequency oscillatory ventilation in an animal model. Prospective randomized animal trial. Eighteen Yorkshire swine. Three groups of six animals each were investigated: control (high frequency oscillatory ventilation alone), low dose perflubron (high frequency oscillatory ventilation plus perfluoro-octyl bromide [PFOB]-Lo, 1.5 mL/kg), and high dose perflubron (high frequency oscillatory ventilation plus PFOB-Hi, 3 mL/kg). Lung injury was induced with repeated saline lavage and amplified for 1 hr using large tidal volumes. Perflubron (Alliance, CA) or a sham dose (room air) was administered with bronchoscopic guidance. The animals were transitioned to high frequency oscillatory ventilation starting at a mean airway pressure of 15 cm H2O. Mean airway pressure was increased (inflation phase) by 5 cm H2O every 15 mins to a maximum mean airway pressure of 40 cm H2O. During the deflation phase, mean airway pressure was reduced by 5 cm H2O every 15 mins to a mean airway pressure of 15 cm H2O. Oxygenation was improved and pulmonary shunt fraction was reduced for PFOB-Hi compared with the control group only at a mean airway pressure of 15 and 20 cm H2O. At a maximal mean airway pressure of 40 cm H2O, oxygenation was not different between the groups, but pulmonary artery pressures were elevated in both PFOB-groups compared with the control group. During the deflation phase, oxygenation, pulmonary shunt fraction, and pulmonary artery pressures were adversely affected by PFOB-Hi and PFOB-Lo. Although PFOB-Hi compared with the control group improved oxygenation and reduced pulmonary shunt fraction only during the first pressure steps of a formal stepwise recruitment maneuver during high frequency oscillatory ventilation, this effect was not sustained during maximal recruitment. During the deflation phase, both PFOB groups were associated with worse gas exchange compared with the control group. PFOB also produced significant pulmonary hypertension in comparison with the control group. | 18,838,935 |
Molecular effects of exercise in patients with inflammatory rheumatic disease. | Exercise is now known to be beneficial for patients with inflammatory rheumatic disease. In patients with rheumatoid arthritis, exercise can improve physical performance, cardiorespiratory fitness and muscle strength, and reduce disease activity and systemic inflammation, as evidenced by reductions in erythrocyte sedimentation rate and other systemic markers of inflammation. Similar effects on physical performance and cardiorespiratory fitness have been observed in patients with polymyositis and dermatomyositis. Improved muscle performance in these patients is associated with an increased ratio of type I : type II muscle fibers and increased cross-sectional area of type II muscle fibers, suggesting that myositis-affected muscle retains the ability to respond to exercise. In addition, resistance exercise training can reduce the expression of genes involved in inflammation and fibrosis in patients with myositis, and in vitro mechanical loading of chondrocytes can suppress the expression of proinflammatory cytokines, indicating that exercise can also reduce inflammation in the local tissue environment. Further studies of the systemic and local responses underlying exercise-associated improvement in muscle performance, soft tissue integrity and health outcomes are warranted. | 18,839,010 |
GM-CSF deficiency delays neointima formation in a normolipidemic mouse model of endoluminal endothelial damage. | Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been implicated in atherogenesis and has been shown to have both pro- and antiatherogenic properties. Neointimal thickening is a prominent feature of early atherogenesis. This study aimed to examine the role of GM-CSF in neointimal formation induced by endothelial injury using a GM-CSF(-/-) mouse model. Neointimal thickening was induced by endothelial damage in the common iliac arteries of normolipidemic C57Bl/6 (wild-type) and GM-CSF(-/-) mice. Arteries were collected weekly for 3-7 weeks following surgery. A significant delay in neointimal formation in the GM-CSF(-/-) compared with wild-type mice was detected by morphometric analysis of the intimal area. Neointimal size was approximately 10% smaller in GM-CSF(-/-) mice at 4-6 weeks post-surgery, compared with wild-type mice. The neointima was composed predominantly of smooth muscle cells and there was no difference in the extent of endothelial cell coverage between the wild-type and GM-CSF(-/-) mice. Using immunohistochemistry, reduced macrophages (F4/80(+) cells), proliferating cells (proliferating cell nuclear antigen (PCNA)(+) cells) and platelet-derived growth factor-B were detected within the arteries of GM-CSF(-/-) mice compared with wild types at 4 weeks post-surgery. GM-CSF(-/-) mice had reduced connective tissue within the neointima compared with wild types at 5 weeks post-surgery, determined by trichrome staining. We conclude that GM-CSF deficiency reduces neointimal formation in a normolipidemic model, primarily due to reduced macrophage recruitment. | 18,839,015 |
Transurethral Resection of Bladder Tumor (TUR-BT) then Concomitant Radiation and Cisplatin Followed by Adjuvant Gemcitabine and Cisplatin in Muscle Invasive Transitional Cell Carcinoma (TCC) of the Urinary Bladder. | To evaluate the efficacy, safety, and tolerance of bladder preservation trimodality protocol combining maximal transurethral resection of bladder tumor (TURBT) with concomitant chemoradiation (CCRT) followed by adjuvant chemotherapy in patients with muscle invasive transitional cell carcinoma (TCC) of the bladder. Between January 2004 and May 2006, 40 patients with invasive TCC (T2-T4a) presented to the Radiation Oncology and Urosurgery departments - Ain Shams University hospitals and were enrolled in this prospective phase II study. Patients were treated using concurrent cisplatin and 45Gy radiotherapy (induction phase) after maximal TUR-BT. Patients were reevaluated 2 weeks after induction CCRT, by cystoscopy, repeated biopsy and urine cytology. Those with complete pathologic response (CR) received consolidation CCRT to 64.8Gy. Patients with less than CR were advised to undergo radical cystectomy (RC). Four cycles of adjuvant gemcitabine 1250mg/m2 on days 1 and 8 and cisplatin 70mg/m2 on day 1, repeated every 3 weeks, were given following definitive therapy. Twenty-four patients achieved CR after initial 45Gy CCRT, 22 of them received additional consolidation CCRT. Eight of 14 patients who did not achieve CR after induction CCRT underwent RC. A total of 30 patients (75%) received adjuvant chemotherapy. Twenty percent (20%) and 13.7% of patients experienced at least one severe (grade 3) toxicity during induction and consolidation phase of CCRT, respectively, mainly neutropenia, cystitis, proctatitis and nausea and vomiting, while 46% experienced at least one severe (grade 3 or 4) toxicity during adjuvant chemotherapy, mainly neutropenia (32%), thrombocytopenia (11%) and nausea and vomiting (29%). Local and/or regional failure was recorded in 40% of patients and distant metastasis was reported in 25%. Eighteen patients (45%) retained functioning and healthy urinary bladder at the end of follow-up. The 2-year actuarial survival and progression free survival (PFS) were 67% (95% CI 52.2%-82.7%) and 58% (95% CI 42.3%-74.0%), respectively. There was significantly better 2 year survival for patients having complete TUR-BT before CCRT. Trimodality approach is a reasonable and safe alternative to RC with manageable toxicities. Longer follow-up with a larger number of patients is necessary to assess its impact on overall and disease-free survival. Key Words: Bladder cancer , Chemoradiotherapy , Cisplatin , Gemcitabine. | 18,839,038 |
Estimated drug overdose deaths averted by North America's first medically-supervised safer injection facility. | Illicit drug overdose remains a leading cause of premature mortality in urban settings worldwide. We sought to estimate the number of deaths potentially averted by the implementation of a medically supervised safer injection facility (SIF) in Vancouver, Canada. The number of potentially averted deaths was calculated using an estimate of the local ratio of non-fatal to fatal overdoses. Inputs were derived from counts of overdose deaths by the British Columbia Vital Statistics Agency and non-fatal overdose rates from published estimates. Potentially-fatal overdoses were defined as events within the SIF that required the provision of naloxone, a 911 call or an ambulance. Point estimates and 95% Confidence Intervals (95% CI) were calculated using a Monte Carlo simulation. Between March 1, 2004 and July 1, 2008 there were 1004 overdose events in the SIF of which 453 events matched our definition of potentially fatal. In 2004, 2005 and 2006 there were 32, 37 and 38 drug-induced deaths in the SIF's neighbourhood. Owing to the wide range of non-fatal overdose rates reported in the literature (between 5% and 30% per year) we performed sensitivity analyses using non-fatal overdose rates of 50, 200 and 300 per 1,000 person years. Using these model inputs, the number of averted deaths were, respectively: 50.9 (95% CI: 23.6-78.1); 12.6 (95% CI: 9.6-15.7); 8.4 (95% CI: 6.5-10.4) during the study period, equal to 1.9 to 11.7 averted deaths per annum. Based on a conservative estimate of the local ratio of non-fatal to fatal overdoses, the potentially fatal overdoses in the SIF during the study period could have resulted in between 8 and 51 deaths had they occurred outside the facility, or from 6% to 37% of the total overdose mortality burden in the neighborhood during the study period. These data should inform the ongoing debates over the future of the pilot project. | 18,839,040 |
Controlling firearms use in Australia: has the 1996 gun law reform produced the decrease in rates of suicide with this method? | Observed reductions in firearm suicides in Australia have been linked to the 1997 national firearms agreement (NFA) introduced following the 1996 Port Arthur massacre. The NFA placed strong access restrictions on firearms. To assess the impact of legislative restrictions on the incidence of firearm suicide in Queensland and explore alternative or contributory factors behind observed declines. The Queensland suicide register (QSR) provided detailed information on all male suicides in Queensland (1990-2004), with additional data for Australia (1968-2004) accessed from other official sources. Trends in suicide rates pre/post NFA, and in method selection, were assessed using negative binomial regressions. Changing method selection patterns were examined using a cohort analysis of 5 years of age classes for Australian males. The observed reduction in firearms suicides was initiated prior to the 1997 introduction of the NFA in Queensland and Australia, with a clear decline observed in Australian figures from 1988. No significant difference was found in the rate pre/post the introduction of the NFA in Queensland; however, a significant difference was found for Australian data, the quality of which is noticeably less satisfactory. A marked age-difference in method choice was observed through a cohort analysis demonstrating both time and age influences. Within sequential birth cohorts, rates of firearms suicides decreased in younger males but increased in hanging suicides; this trend was far less marked in older males. The implemented restrictions may not be responsible for the observed reductions in firearms suicide. Data suggest that a change in social and cultural attitudes could have contributed to the shift in method preference. | 18,839,044 |
The effect of metformin on leptin in obese patients with type 2 diabetes mellitus and nonalcoholic fatty liver disease. | Insulin resistance is a major feature of type 2 diabetes mellitus, obesity and nonalcoholic fatty liver disease (NAFLD). Several studies pointed out the possible role of increased leptin in NAFLD in humans. The aim of this study is to determine the effect of metformin on plasma leptin levels in obese patients with type 2 diabetes mellitus and NAFLD compared with lifestyle interventions. Thirty-four obese patients with newly diagnosed type 2 diabetes mellitus were prospectively followed for 6 months. All patients had ultrasonographic evidence of NAFLD at baseline. The patients were randomized into two groups: group 1 (n = 15) followed lifestyle changes only and group 2 (n = 19) received metformin (1,700 mg/day). At the end of treatment, BMI, WHR, HbA1c, fasting glucose, leptin, HOMA-IR, alanine aminotransferase values decreased in both groups. No significant difference in the end-points was observed between two groups. Only in group 2, LDL decreased and HDL increased significantly. Liver echogenity decreased significantly at the end of study in both groups. The percentage of patients who no longer had evidence of NAFLD was not significantly different between the groups (20% of patients on lifestyle intervention vs. 16% of patients on metformin). The data demonstrate that, metformin and lifestyle interventions equally affected the plasma leptin levels, BMI and degree of NAFLD in obese patients with type 2 diabetes mellitus. In addition, the effects of metformin on the variables were not found to be mediated by leptin. | 18,839,053 |
Unique microstructures and podocytic infolding in glomerular basement membrane associated with collagen diseases: a report of three cases. | Unique renal histopathological appearances, consisting of podocytic infolding and microstructures in the glomerular basement membrane (GBM) were identified in the renal biopsies from three patients with collagen diseases such as systemic lupus erythematosus (lupus nephritis, class II) and Sjögren's syndrome. In each case, the GBM contained microstructures, including microspheres and microtubular structures, accompanied by podocytic infolding into the GBM when examined by electron microscope. The size of the microstructures in the GBM ranged from 40 to 160 nm. Glomerular endothelial cells also seemed to be infolded in the GBM in a case with lupus nephritis. The response to glucocorticoid therapy was favorable in two cases. The cause of these morphological changes in the GBM might be associated with autoimmune disorders. | 18,839,060 |
A case of systemic lupus erythematosus showing invagination of the podocyte into the glomerular basement membrane: an electron microscopic observation of a repeated-renal biopsy. | A case of systemic lupus erythematosus (SLE) showing invagination of glomerular epithelial cells into the glomerular basement membrane (GBM) has been reported. The patient was a 30-year-old woman who was diagnosed with SLE at the age of 25 and had been medicated with corticosteroid. At the age of 30, she was re-admitted into our hospital because of the relapse of lupus nephritis. Renal biopsy was performed twice: at the onset of SLE and the second admission. Morphologically, the results of the first and second renal biopsies were compatible with the classification of lupus nephritis class II. Immunofluorescent study revealed the mesangial deposition of IgG, IgA, C1q, C3 and membrane attack complex (MAC) in two renal biopsies. Especially, in the second renal biopsy, numerous vesicular structures composed of a unit membrane going into the epithelial site of the GBM were observed by electron microscopy (EM), but not in the first renal biopsy. Moreover, observations of serial sections of EM suggested that these vesicular structures were invaginated into the GBM and derived from a part of the podocytes. | 18,839,064 |
Two-photon imaging of capillary blood flow in olfactory bulb glomeruli. | Two-photon laser scanning microscopy (TPLSM) is an efficient tool to study cerebral blood flow (CBF) and cellular activity in depth in the brain. We describe here the advantages and weaknesses of the olfactory bulb as a model to study neurovascular coupling using TPLSM. By combining intra- and extracellular recordings, TPLSM of CBF in individual capillaries, local application of drugs, we show that odor triggers odorant-specific and concentration-dependent increases in CBF. We also demonstrate that activation of neurons is required to trigger blood flow responses. | 18,839,088 |
Magnetoencephalography (MEG). | Magnetoencephalography (MEG) encompasses a family of non-contact, non-invasive techniques for detecting the magnetic field generated by the electrical activity of the brain, for analyzing this MEG signal and for using the results to study brain function. The overall purpose of MEG is to extract estimates of the spatiotemporal patterns of electrical activity in the brain from the measured magnetic field outside the head. The electrical activity in the brain is a manifestation of collective neuronal activity and, to a large extent, the currency of brain function. The estimates of brain activity derived from MEG can therefore be used to study mechanisms and processes that support normal brain function in humans and help us understand why, when and how they fail. | 18,839,092 |
Real-time PCR analysis for blood cell lineage specific markers. | We here describe the methods for the isolation of distinct hematopoietic subpopulations, as defined by their immune phenotype by fluorescence-activated cell sorting, and how these cells can be analyzed even at a single-cell level for the gene expression of a number of transcription factors and other differentiation markers. | 18,839,120 |
Design, conduct, analysis and reporting of a multi-national placebo-controlled trial of activated protein C for persistent septic shock. | The role of drotrecogin alfa (activated) (DAA) in severe sepsis remains controversial and clinicians are unsure whether or not to treat their patients with DAA. In response to a request from the European Medicines Agency, Eli Lilly will sponsor a new placebo-controlled trial and history suggests the results will be subject to great scrutiny. An academic steering committee will oversee the conduct of the study and will write the study manuscripts. The steering committee intends that the study will be conducted with the maximum possible transparency; this includes publication of the study protocol and a memorandum of understanding which delineates the role of the sponsor. The trial has the potential to provide clinicians with valuable data but patients will only benefit if clinicians have confidence in the conduct, analysis and reporting of the trial. This special article describes the process by which the trial was developed, major decisions regarding trial design, and plans for independent analysis, interpretation and reporting of the data. | 18,839,141 |
In vivo flexion and kinematics of the knee after TKA: comparison of a conventional and a high flexion cruciate-retaining TKA design. | This study investigated the in vivo 6DOF knee kinematics and tibiofemoral contact location after total knee arthroplasty using a conventional and a high flexion cruciate retaining component (15 NexGen CR, 11 NexGen CR-Flex). Each patient performed a single-leg lunge while being imaged by a dual fluoroscopic imaging system. Data were analyzed at hyperextension, 0 degrees to 90 degrees in 15 degrees intervals, and at maximum flexion. The average maximum weight-bearing flexion for all the CR patients was 110.1 degrees +/- 13.4 degrees , and for all the CR-Flex patients was 108.2 degrees +/- 13.2 degrees . No difference was seen in the maximum flexion achieved by the patients, and the kinematics demonstrated by the groups was similar. However, at high flexion, the tibiofemoral articulating surfaces were more conforming in the CR-Flex design than the CR design, suggesting that the use of the high flexion component improved the tibiofemoral contact environment at high flexion in patients who could achieve high flexion. | 18,839,144 |
Comparison of ultrasound-, palpation-, and scintigraphy-guided steroid injections in the treatment of plantar fasciitis. | The aim of the study was to compare the efficacies of steroid injections guided by scintigraphy, ultrasonography, and palpation in plantar fasciitis. A total of 35 heels of 27 patients were randomly assigned to three steroid injection groups: palpation-guided (pg), ultrasound-guided (ug), and scintigraphy-guided (sg). Patients were evaluated for pain intensity before the injections and at the last follow-up of 25.3 months with a 100-mm visual analog scale (VAS). There were significant improvements in plantar fascia thickness, fat pad thickness, and VAS. Among the three groups of ug-pg, ug-sg, and pg-sg there were no statistically significant differences after treatment (P = 0.017, MWU = 36.5; P = 0.023, MWU = 29.5; and P = 0.006, MWU = 13, respectively). The ug, pg, and sg injections were effective in the conservative treatment of plantar fasciitis. We are of the opinion that steroid injections should be performed, preferably with palpation or ultrasonographic guidance. | 18,839,190 |
Outcome of radiotherapy in T1 glottic carcinoma: a population-based study. | We evaluated the radiation outcome and prognostic factors in a population-based study of early (T1N0M0) glottic carcinoma. Survival parameters and prognostic factors were evaluated by uni- and multivariate analysis in 316 consecutive irradiated patients with T1 glottic carcinoma in the Comprehensive Cancer Center West region of the western Netherlands. Median follow-up was 70 months (range 1-190 months). Five and ten-year local control was 86 and 84%. Disease specific survival was 97% at 5 and 10 years. In multivariate analysis, pre-existent laryngeal hypertrophic laryngitis was the only predictive factor for local control (relative risk = 3.0, P = 0.02). Comorbidity was prognostic for overall survival. No factor was predictive for disease specific survival. Pre-existent laryngeal hypertrophic laryngitis is a new risk factor associated with reduced local control in T1 glottic carcinoma treated with radiotherapy. | 18,839,197 |
The time course of presaccadic attention shifts. | The dynamics of the allocation of attention during the preparation of saccadic eye movements was studied in a dual task paradigm. As the primary task, participants had to perform a saccade to letter-like items arranged on a clock face. The secondary task was a 2AFC discrimination task in which a discrimination target (DT) ('E' or '3') was presented among distractors, either at the saccade goal, or at a spatially separate, precued location. In the first experiment, the position of the DT was kept constant within an experimental block, while the saccade target location varied. In the second experiment, the location of the DT was varied while the saccade target remained the same within a block. The data demonstrate that attentional dynamics differs between the experiments--attention can shift to the saccade goal early or late during the saccade preparation period, depending on the task. Immediately before saccade onset, however, discrimination performance at the location of the saccade target is always superior to other locations, arguing for a strict and selective coupling between saccade preparation and attention. | 18,839,208 |
Gastroenteropancreatic neuroendocrine tumors: indications for and pitfalls of frozen section examination. | Gastroenteropancreatic neuroendocrine tumors constitute a heterogeneous group of neoplasms. Surgical resection remains the only curative treatment. Frozen section examination is requested by the surgeon in a large variety of surgical situations, but its use differs greatly according to the location of the tumor and the type of surgery performed. The objective of this review is to describe the main indications for and pitfalls of frozen section examination of gastroenteropancreatic neuroendocrine tumors. | 18,839,209 |
Tree diversity, composition, forest structure and aboveground biomass dynamics after single and repeated fire in a Bornean rain forest. | Forest fires remain a devastating phenomenon in the tropics that not only affect forest structure and biodiversity, but also contribute significantly to atmospheric CO2. Fire used to be extremely rare in tropical forests, leaving ample time for forests to regenerate to pre-fire conditions. In recent decades, however, tropical forest fires occur more frequently and at larger spatial scales than they used to. We studied forest structure, tree species diversity, tree species composition, and aboveground biomass during the first 7 years since fire in unburned, once burned and twice burned forest of eastern Borneo to determine the rate of recovery of these forests. We paid special attention to changes in the tree species composition during burned forest regeneration because we expect the long-term recovery of aboveground biomass and ecosystem functions in burned forests to largely depend on the successful regeneration of the pre-fire, heavy-wood, species composition. We found that forest structure (canopy openness, leaf area index, herb cover, and stem density) is strongly affected by fire but shows quick recovery. However, species composition shows no or limited recovery and aboveground biomass, which is greatly reduced by fire, continues to be low or decline up to 7 years after fire. Consequently, large amounts of the C released to the atmosphere by fire will not be recaptured by the burned forest ecosystem in the near future. We also observed that repeated fire, with an inter-fire interval of 15 years, does not necessarily lead to a huge deterioration in the regeneration potential of tropical forest. We conclude that burned forests are valuable and should be conserved and that long-term monitoring programs in secondary forests are necessary to determine their recovery rates, especially in relation to aboveground biomass accumulation. | 18,839,212 |
Toward using delta13C of ecosystem respiration to monitor canopy physiology in complex terrain. | In 2005 and 2006, air samples were collected at the base of a Douglas-fir watershed to monitor seasonal changes in the delta13CO2 of ecosystem respiration (delta13C(ER)). The goals of this study were to determine whether variations in delta13C(ER) correlated with environmental variables and could be used to predict expected variations in canopy-average stomatal conductance (Gs). Changes in delta13C(ER) correlated weakly with changes in vapor pressure deficit (VPD) measured 0 and 3-7 days earlier and significantly with soil matric potential (psi(m)) (P value <0.02) measured on the same day. Midday G (s) was estimated using sapflow measurements (heat-dissipation method) at four plots located at different elevations within the watershed. Values of midday Gs from 0 and 3-7 days earlier were correlated with delta13C(ER), with the 5-day lag being significant (P value <0.05). To examine direct relationships between delta13C(ER) and recent Gs, we used models relating isotope discrimination to stomatal conductance and photosynthetic capacity at the leaf level to estimate values of stomatal conductance ("Gs-I") that would be expected if respired CO2 were derived entirely from recent photosynthate. We compared these values with estimates of Gs using direct measurement of transpiration at multiple locations in the watershed. Considering that the approach based on isotopes considers only the effect of photosynthetic discrimination on delta13C(ER), the magnitude and range in the two values were surprisingly similar. We conclude that: (1) delta13C(ER) is sensitive to variations in weather, and (2) delta13C(ER) potentially could be used to directly monitor average, basin-wide variations in Gs in complex terrain if further research improves understanding of how delta13C(ER) is influenced by post-assimilation fractionation processes. | 18,839,214 |
Measuring glomerular filtration rate in children; can cystatin C replace established methods? A review. | Our aim was to evaluate published methods that use serum cystatin C (s-CysC) for measuring glomerular filtration rate (GFR) in children and to discuss advantages and limitations of s-CysC and of established GFR methods. A comprehensive literature review of clinical studies in children evaluating s-CysC or CysC-based formulas and plasma creatinine or creatinine-based formulas against an exogenous reference method using receiver operating characteristics (ROC) curves or Bland-Altman plots is presented. The comparison of s-CysC with plasma creatinine indicated that s-CysC was superior to plasma creatinine in five of 13 studies; four studies showed no difference, and, in four studies, no statistical comparison was made. Comparison of s-CysC and the Schwartz formula showed that s-CysC was superior to the Schwartz formula in two of seven studies; two studies demonstrated no difference, and, in one study, the Schwartz formula was superior to s-CysC. In two studies no statistical comparison was made. The CysC-based prediction equations all had high accuracy but low agreement when compared with a reference GFR, in the range of 30-40% at best. S-CysC is most likely superior to plasma creatinine and at least equal to creatinine-based formulas. CysC-based prediction equations are at least as good as creatinine-based formulas but cannot replace exogenous methods. | 18,839,216 |
Reversal of hypercalcemic acute kidney injury by treatment with intravenous bisphosphonates. | We present the details of three children with hypercalcemia-induced acute kidney injury (AKI). After traditional therapy with fluids, loop diuretics, steroids and calcitonin had failed to correct the hypercalcemia, they were given treatment with low doses of intravenous (i.v.) pamidronate, which resulted in normalization of serum calcium and kidney function. In one child Doppler renal ultrasound revealed dampened arterial blood flow, which resolved with normalization of serum calcium. On the basis of cumulative data and our experience, we suggest that i.v. application of bisphosphonates be moved from the second to the first line of treatment of hypercalcemic AKI. | 18,839,218 |
Palonosetron (Aloxi) and dexamethasone for the prevention of acute and delayed nausea and vomiting in patients receiving multiple-day chemotherapy. | The objective of this study was to determine the efficacy of palonosetron combined with dexamethasone in prevention of acute and delayed chemotherapy-induced nausea and vomiting (CINV) in patients receiving multiple-day chemotherapy and the efficacy of a second dose of palonosetron in treating breakthrough emesis. Forty-six patients treated with multiple-day chemotherapy for hematologic malignancies received palonosetron as prophylaxis for CINV on the first day of chemotherapy and dexamethasone throughout the entire period of chemotherapy. If breakthrough emesis occurred, a second dose of palonosetron was administered after 72 h following the first administration. The results were retrospectively compared to group of patients with similar clinical characteristics undergoing similar multiple-day chemotherapy. This group had received single-dose ondansetron as CINV prophylaxis on the first day of chemotherapy plus dexamethasone throughout the entire period of chemotherapy and metoclopramide for breakthrough emesis. One hundred eighty and 173 chemotherapy cycles were administered in the palonosetron and ondansetron groups, respectively. Nausea and vomiting were absent in 80% of patients of the palonosetron group and 60% of the control group (p < 0.05). In the palonosetron group, 67% of patients who experienced CINV were successfully rescued by a second dose of palonosetron, while in the ondansetron group, only 22% showed a no CINV after metoclopramide treatment (p = 0.04). The present results appear to be encouraging in terms of complete prophylaxis of CINV and treatment of breakthrough emesis in the setting of multiple-day chemotherapy. | 18,839,220 |
Posterior lumbar interbody fusion using rhBMP-2. | The use of biological technologies for the treatment of degenerative spinal diseases has undergone rapid clinical and scientific development. BMP strategies have gained wide support for an inherent potential to improve the ossification process. It has been extensively studied in combination with various techniques for spinal stabilisation from both anterior and posterior approach. We studied the fusion process after implantation of rhBMP-2 in 17 patients with degenerative lumbar spine diseases in combination with dorsal fixation with pedicle screws and poly-ether-ether-ketone (PEEK) interbody cages. We used 12 mg rhBMP-2 carried by collagen sponge, 6 mg in every cage. Patient follow up consisted of pre-operative radiographic and clinical evaluation. Similar post-operative evaluations were performed at 3 and 6 months. Clinical assessment demonstrated clear improvement in all patients despite evidence of vertebral endplate osteoclastic activity in the 3-month radiographs. The 6-month radiograph, however, confirmed evidence of fusion, and no untoward results or outcomes were noted. While previous studies have shown exclusively positive results in both fusion rates and process, our study demonstrated an intermediate morphology at 3 months during the ossification process using Induct Os in combination with peek-cages using a PLIF-technique. The transient resorption of bone surrounding the peek cage did not result in subsidence, pain or complication, and fusion was reached in all cases within a 6-month-controlled evaluation. Although there was no negative influence on clinical outcome, the potential for osteoclastic or metabolic resorption bears watching during the post-surgical follow up. | 18,839,225 |
Grading of degenerative disk disease and functional impairment: imaging versus patho-anatomical findings. | Degenerative instability affecting the functional spinal unit is discussed as a cause of symptoms. The value of imaging signs for assessing the resulting functional impairment is still unclear. To determine the relationship between slight degrees of degeneration and function, we performed a biomechanical study with 18 multisegmental (L2-S2) human lumbar cadaveric specimens. The multidirectional spinal deformation was measured during the continuous application of pure moments of flexion/extension, bilateral bending and rotation in a spine tester. The three flexibility parameters neutral zone, range of motion and neutral zone ratio were evaluated. Different grading systems were used: (1) antero-posterior and lateral radiographs (degenerative disk disease) (2) oblique radiographs (facet joint degeneration) (3) macroscopic and (4) microscopic evaluation. The most reliable correlation was between the grading of microscopic findings and the flexibility parameters; the imaging evaluation was not as informative. | 18,839,226 |
Assessing the effectiveness of a constructed Arctic stream using multiple biological attributes. | Objective assessment of habitat compensation is a central yet challenging issue for restoration ecologists. In 1997, a 3.4-km stream channel, designed to divert water around an open pit diamond mine, was excavated in the Barrenlands region of the Canadian Arctic to create productive stream habitat. We evaluated the initial success of this compensation program by comparing multiple biological attributes of the constructed stream during its first three years to those of natural reference streams in the area. The riparian zone of the constructed stream was largely devoid of vegetation throughout the period, in contrast to the densely vegetated zones of reference streams. The constructed stream also contained lower amounts of woody debris, coarse particulate organic matter (CPOM), and epilithon; had lower coverage by macrophytes and bryophytes; and processed leaf litter at a lower rate than reference streams. Species richness and densities of macroinvertebrates were consistently lower in the constructed stream compared to natural streams. This contributed to differences in macroinvertebrate assemblage structure throughout the period, although assemblages showed some convergence by year 3. The effectiveness of the constructed stream to emulate natural streams varied somewhat depending on the biological attribute being evaluated. Assessments based on individual attributes showed that minimal to moderate levels of similarity between the constructed stream and natural streams were achieved. A collective assessment of all biological and ecosystem attributes suggested that the constructed stream was not a good surrogate for natural streams during these first years. Additional time would be required before many characteristics of the constructed stream would resemble those of reference streams. Because initial efforts to improve fish habitat in the constructed stream focused on physical structures (e.g., weirs, vanes, rock, groins), ecological factors limiting fish growth were not considered and likely constrained success. We suggest that a greater focus on organic characteristics and vegetation within the stream and its riparian zone could have accelerated compensation. The addition of woody debris and CPOM, combined with planting of shrubs and herbs along the stream, should provide a source of allochthonous matter for the biotic community while large cobble and boulders should improve the physical stability of stream system, protecting its organic components. | 18,839,240 |
Biotransformation of 2,4,6-trinitrotoluene by pure culture ruminal bacteria. | Twenty-one ruminal bacteria species were tested for their ability to degrade 2,4,6-trinitrotoluene (TNT) within 24 h. Butyrivibrio fibrisolvens, Fibrobacter succinogenes, Lactobacillus vitulinus, Selenomonas ruminantium, Streptococcus caprinus, and Succinivibrio dextrinosolvens were able to completely degrade 100 mg/L TNT, with <5% of the original TNT recovered as diaminonitrotoluene metabolites. Eubacterium ruminantium, Lactobacillus ruminis, Ruminobacter amylophilus, Streptococcus bovis, and Wolinella succinogenes were able to completely degrade 100 mg/L TNT, with 23-60% of the TNT recovered as aminodinitrotoluene and/or diaminonitrotoluene metabolites. Clostridium polysaccharolyticum, Megasphaera elsdenii, Prevotella bryantii, Prevotella ruminicola, Ruminococcus albus, and Ruminococcus flavefaciens were able to degrade 80-90% of 100 mg/L TNT. Desulfovibrio desulfuricans subsp. desulfuricans, Prevotella albensis, and Treponema bryantii degraded 50-80% of the TNT. Anaerovibrio lipolytica was completely inhibited by 100 mg/L TNT. These results indicate that a variety of rumen bacteria is capable of transforming TNT. | 18,839,246 |
Effects of fertilization and fungal and insect attack on systemic protein defenses of austrian pine. | Despite their economic and ecological importance, defense responses of conifers to pests are little understood. In a 3-year experiment, we monitored systemic fungal (Diplodia pinea)- and insect (Neodiprion sertifer)-induced defense protein activities and total soluble proteins in needles and phloem of Austrian pine (Pinus nigra) across a soil fertility gradient. In both years, total soluble protein content of foliage and phloem declined with increasing fertility across induction treatments, while defensive protein activities generally increased with increasing fertility. In 2005, total soluble protein content in branch phloem was increased by fungal inoculation of the stem. Peroxidase activity was suppressed in needles by insect defoliation in 2006, while polyphenol oxidase activity was systemically induced in branch phloem by insect attack in 2005. Trypsin inhibitor activities in phloem did not respond to any induction or fertility treatment. Nutritive quality of Austrian pine tissue declined with increasing fertility, while several protein-based defenses simultaneously increased. | 18,839,253 |
Identification of novel C(20) and C (22) trienoic acids from arctiid and geometrid female moths that produce polyenyl Type II Sex pheromone components. | Gas chromatography-mass spectrometry (GC-MS) and GC-electroantennographic detection (EAD) analyses of the sex pheromone extract from a wasp moth, Syntomoides imaon (Lepidoptera: Arctiidae: Syntominae), showed that virgin females produced (Z,Z,Z)-3,6,9-henicosatriene and (Z,Z,Z)-1,3,6,9-henicosatetraene with a trace amount of their C(20) analogs. Identification of the chemical structures was facilitated by comparison with authentic standards and the double-bond positions were confirmed by dimethyl disulfide derivatization of monoenes produced by a diimide reduction. In a field test in the Yonaguni-jima Islands, males of the diurnal species were captured in traps baited with a 1:2 mixture of the above-described synthetic C(21) polyenes. Lipids were extracted from the abdominal integument and its associated oenocytes and peripheral fat bodies. Following derivatization, fatty acid methyl esters (FAMEs) were fractionated by HPLC equipped with an ODS column, and methyl (Z,Z,Z)-11,14,17-icosatrienoate and (Z,Z,Z)-13,16,19-docosatrienoate were identified by GC-MS. These novel C(20) and C(22) acid moieties are longer-chain analogs of linolenic acid, (Z,Z,Z)-9,12,15-octadecatrienoic acid. They are presumed to be biosynthetic precursors of the S. imaon pheromone because the C(21) trienyl component might be formed by decarboxylation of the C(22) acid. On the other hand, the C(20) acid, but not the C(22) acid, was found in FAMEs of Ascotis selenaria cretacea (Lepidoptera: Geometridae), which secretes C(19) pheromone components, (Z,Z,Z)-3,6,9-nonadecatriene and the monoepoxy derivative, indicating that different systems of the chain elongation might play an important role in developing species-specific communication systems mediated with polyunsaturated hydrocarbons and/or epoxy derivatives, components of Type II lepidopteran sex pheromones. | 18,839,254 |
Spontaneous dissection of internal carotid artery masquerading as angioedema. | Spontaneous dissection of the internal carotid artery usually presents with stroke-like symptoms secondary to ischemia in its vascular territory, as well as local signs and symptoms, which may include head, face or neck pain, Horner's syndrome, pulsatile tinnitus, and cranial nerve palsies. We report a case of a 44-year-old healthy white male who presented with tongue swelling mimicking angioedema as an unusual manifestation of spontaneous dissection of the internal carotid artery. Two weeks after the initial presentation, the patient returned with similar symptoms and slurred speech. Upon physical examination, he was noted to have isolated left-sided hypoglossal nerve palsy. Subsequent diagnostic imaging revealed segmental narrowing of the left internal carotid artery. The appearance was consistent with the presence of a spontaneous internal carotid artery dissection with associated pseudoaneurysm formation. | 18,839,259 |
Managing flexion knee deformity using a circular frame. | Knee flexion deformity can cause marked physical disability. Acute correction, whether nonoperative or operative, may lead to serious complications. We treated 50 patients (71 knees) between 1994 and 2002 with the Ilizarov external fixator. The deformity was gradually corrected using Ilizarov principles. Of the 50 patients, 29 were affected unilaterally and 21 bilaterally. In 15 patients, there were associated deformities. In no patient did we surgically release soft tissues; in two patients with arthrodesed or congenitally fused knees, we performed osteotomy before distraction. All patients were assessed clinically and radiographically. We assessed knee flexion angle, range of motion, stability, presence of pain, and healing index. After a minimum followup of 1 year (mean 3.7 years; range, 1-8 years), 18 of 20 of the preoperatively nonambulatory patients having bilateral surgery could walk at last followup. Complications included pin tract infection in all patients, knee subluxation in three patients, and fracture related to treatment in seven patients. We believe gradual correction using a circular frame an effective method to treat flexion knee contractures. In patients with bilateral deformities, improvement in functional activity may be expected in most patients. Level IV, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence. | 18,839,263 |
A case of ANCA-associated systemic vasculitis induced by atorvastatin. | We present a 45-year-old male patient who presented to Accident and Emergency department with a 6-week history of pain and stiffness involving his bilateral legs. Both calves were markedly tender, and he was not able to bear weight. He also complained of numbness involving his left big toe for a few days, which later spread to involve his arms, and tinnitus and hearing loss in his left ear. There were no respiratory, gastrointestinal or urinary symptoms. He had a background history of hypercholesterolemia and was treated with atorvastatin 10 mg for 6 months. His initial investigations showed markedly increased inflammatory markers, and serum antineutrophil cytoplasmic antibody (ANCA) was markedly positive at a titre of 1:160 (P-ANCA). Electromyography and muscle biopsy showed myopathic features. A diagnosis of drug-induced ANCA-associated vasculitis (on the basis of mononeuritis multiplex, sensorineural hearing loss and markedly increased anti-myeloperoxidase (MPO) ANCA) and statin-induced distal myopathy was made. He was treated with three 500 mg doses of methylprednisolone, followed by slowly tapering dose of oral corticosteroids from 30 mg once daily (OD). He was also started on azathioprin (2.5 mg/kg). He had a dramatic improvement of his myalgia, hearing loss and sensory symptoms and went into complete clinical remission. His inflammatory markers rapidly returned to normal, and MPO-ANCA normalised within 3 months of starting immunosuppressive therapy and remained negative on further testing. He is currently on a tapering regimen of corticosteroids (7 mg OD), and after weaning him off corticosteroids, we plan to slowly taper his azathioprin. | 18,839,266 |
Evaluation of groundwater resources in a tiny Andrott Island, Union Territory of Lakshadweep, India. | Lakshadweep is a group of 36 coral islands scattered in the Arabian Sea off the western coast of India. On such small tiny islands, groundwater is the only source of fresh water for the islanders. Due to the growing population on these islands, demand for fresh water is also increasing and on the other side the peculiar hydrologic, geologic and geomorphic features restrict the availability of groundwater. Therefore, a proper understanding of the groundwater condition is important in order to meet this increasing demand and also to formulate future development and management strategies. Detailed hydrogeological, geophysical and hydrochemical studies have been carried out to identify potential fresh groundwater resources and quantify vulnerable parts of Andrott Island, Union Territory of Lakshadweep. Systematic collection and analysis of hydrological, geophysical and hydrochemical data reveal that fresh groundwater is only available between 2.5 to 5.0 m depths and provide an early sign of deterioration in groundwater quality in the peripheral parts of eastern and western coasts of this island. It suggests immediate measures for arresting the deterioration in groundwater quality as well as augmentation for restoration of aquifer in some parts of the island. | 18,839,323 |
Resistin induces rat insulinoma cell RINm5F apoptosis. | Beta-cell apoptosis induced by adipokines may result in beta-cell dysfunction in type 2 diabetes. Resistin, an adipokine-linked obesity with type 2 diabetes, impairs glucose-stimulated insulin secretion (GSIS) in beta-cells. Presently, the effects of resistin on rat insulinoma cells RINm5F were examined. Treatment of RINm5F with resistin induced cell damage. Tissue Inhibitor of Metalloproteinase-1 (TIMP-1) protected resistin-mediated cytotoxicity in RINm5F. Incubation with resistin up-regulated caspase-3 activity and induced the formation of a DNA ladder. TIMP-1 attenuated these effects. The molecular mechanism of TIMP-1 inhibition of resistin-mediated cytotoxicity appeared to involve Akt phosphorylation and activation of IkB-alpha phosphorylation. Resistin treatment suppressed Akt phosphorylation and activated IkB-alpha phosphorylation, which could be attenuated by TIMP-1. We conclude that resistin can induce beta-cell apoptosis and that resistin-related beta-cell apoptosis can be prevented by TIMP-1. | 18,839,335 |
RNA isolation from Xenopus inner ear sensory endorgans for transcriptional profiling and molecular cloning. | The amphibian Xenopus offers a unique model system for uncovering the genetic basis of auditory and vestibular function in an organism that is well-suited for experimental manipulation during animal development. However, many procedures for analyzing gene expression in the peripheral auditory and vestibular systems mandate the ability to isolate intact RNA from inner ear tissue. Methods presented here facilitate preparation of high quality inner ear RNA from larval and post-metamorphic Xenopus specimens that can be used for a variety of purposes. We demonstrate that RNA isolated with these protocols is suitable for microarray analysis of inner ear organs, and for cloning of large transcripts, such as those for ion channels. Genetic sequences cloned with these procedures can be used for transient transfection of Xenopus kidney cell lines with GFP fusion constructs. | 18,839,338 |
Personality and EQ-5D scores among individuals with chronic conditions. | Personality is associated with self-rated health, but prior studies have not examined associations with preference-based measures. We hypothesized similar associations would exist with preference-based health. We analyzed baseline data from chronically ill individuals enrolled in a self-management intervention. We conducted regression analyses with the EQ-5D summary index score and dimension scores (mobility, self-care, usual activities, pain/discomfort, anxiety/depression) as dependent variables, The key independent variables were NEO-Five Factor Inventory (NEO-FFI) personality factors (Neuroticism, Conscientiousness, Extraversion, Openness, Agreeableness), adjusting for age, gender, educational level, minority status, and chronic conditions. Of 415 participants, 245 (59%) had > or =2 chronic conditions, 384 (94%) completed the NEO-FFI and 397 (96%) the EQ-5D. After adjustment, Neuroticism was associated with EQ-5D summary index scores [-0.04 per 1 SD increase in Neuroticism (95% CI -0.06, -0.01)]. Neuroticism [AOR 2.99 (95% CI 2.06, 4.35; P < 0.001)] and Openness [1.32 (95% CI 1.00, 1.75; P = 0.05)] were associated with worse anxiety/depression scores, while Conscientiousness was associated with better usual activities scores [0.66 (95% CI 0.49, 0.89; P = 0.01)]. The associations between personality factors and self-rated health appear to extend to preference-based measures. Future studies should explore whether personality affects preference-based health estimates in cost-effectiveness analyses. | 18,839,336 |
In vivo verification of protein interactions in the inner ear by coimmunoprecipitation. | Genomics has provided us with vast amounts of data and thus, the challenge to identify and characterize gene products. Proteomics analysis, using methods such as yeast two-hybrid screenings, isoelectric focusing, and mass spectroscopy, generate potentially useful information. To determine functional relationships between and among proteins, however, the initial data for putative protein interactions must first be validated. One technique, which is considered the gold standard, is coimmunoprecipitation. | 18,839,355 |
Surface plasmon resonance (SPR) analysis of binding interactions of proteins in inner-ear sensory epithelia. | Surface plasmon resonance is an optical technique utilized for detecting molecular interactions. Binding of a mobile molecule (analyte) to a molecule immobilized on a thin metal film (ligand) changes the refractive index of the film. The angle of extinction of light, reflected after polarized light impinges upon the film, is altered, monitored as a change in detector position for the dip in reflected intensity (the surface plasmon resonance phenomenon). Because the method strictly detects mass, there is no need to label the interacting components, thus eliminating possible changes of their molecular properties. We have utilized surface plasmon resonance to study the interaction of proteins of hair cells. | 18,839,357 |
The Norwegian Hip Fracture Register: experiences after the first 2 years and 15,576 reported operations. | The Norwegian Hip Fracture Register was established in January 2005 to collect nationwide information as a basis for improved management of patients with hip fractures. We now report our experience after the first 2 years. After both primary operations and reoperations, the surgeons fill in a standardized 1-page form with information about the patient, the fracture, and the operation. Fractures treated with a total hip arthroplasty are reported to the national arthroplasty register, but are added to the hip fracture register before analyses are performed. 4, 12, and 36 months postoperatively, a standardized questionnaire including health-related quality of life (EQ-5D), visual analog scales concerning pain and patient satisfaction, and Charnley class for functional assessment is sent directly from the register to the patients. To evaluate the completeness of registration, our data were compared with data from the Norwegian Patient Registry (NPR). During the first year of registration, all 55 hospitals treating hip fractures in Norway started to report their hip fracture operations. During 2005, the monthly reporting increased and it stabilized in 2006. 13,251 primary-operated hips (mean age of patients: 80 years; 72% females) and 2,325 reoperations were reported during 2005 and 2006. Compared to the NPR, the completeness of registration was 64% in 2005 and 79% in 2006. 58% of the patients who were alive answered the 4-month questionnaire. The non-responders were older, were more often cognitively impaired, and had a higher degree of comorbidity than the responders. Undisplaced femoral neck fractures (19% of all fractures) were almost exclusively operated with screw osteosynthesis (95%). Dislocated femoral neck fractures (38% of all fractures) were operated with a hemiarthroplasty in 52% of the cases. Osteosynthesis with a hip compression screw was the predominant operation method for trochanteric fractures (81%). After only 2 years, our nationwide system for surveillance of demographics, treatment, and outcome of hip fractures is functioning well. As expected, the response rate for the 4-month questionnaires was relatively low due to the old population with high comorbidity and cognitive impairment. The different treatment methods used for patients in the same groups of fracture types show that there is still no consensus in Norway regarding the treatment of hip fractures. | 18,839,363 |
Hand-made articulating spacers in two-stage revision for infected total knee arthroplasty: good outcome in 30 patients. | The most reliable results when treating an infected total knee arthroplasty have been obtained with a two-stage reimplantation protocol. We have used a simple technique for hand-made spacers and now report the outcome. 30 patients with an infected total knee arthroplasty (TKA) were treated with a 2- stage reimplantation protocol. Spacers were built and customized to the type of defect using only 2 retractors and a high-speed tip burr. Partial weight bearing and discharge from the hospital were encouraged in the time between surgeries. 29 of 30 patients (97%) had successful reimplantations and they were followed for an average of 3 (2-5) years. Range of motion with the articulating spacer averaged 80 degrees (55-100) and 21 of the 30 patients achieved motion greater than 75 degrees . At the latest follow-up, there were no reinfections. According to the Knee Society score (KSS), the results were considered excellent or good in 25 patients, and fair or poor in 4 of the 29 patients with reimplantations. Motion after reimplantation averaged 107 degrees (90-120). One of the key factors related to a successful outcome with a two-stage reimplantation procedure is to keep the joint mobile and functional in the time between surgeries. Hand-made articulating spacers retain most of the advantages of more complex spacers in terms of mobility, pain, bone loss, success, or re-infection rate-with the major advantages of price and universal availability. Limitations related to this technique include potential knee instability, the need to walk with an orthosis, and the risk of subluxations. | 18,839,375 |
Second-look microlaryngoscopy to detect residual carcinoma in patients after laser surgery for T1 and T2 laryngeal cancer. | The presented concept of second-look microlaryngoscopy in patients treated with transoral laser surgery (TLS) for early glottic carcinoma is promising and warrants further studies to evaluate its benefits. Clear surgical margins at the primary site influence the course of the disease in patients with laryngeal carcinoma who undergo TLS. Several factors may lead to a reduced sensitivity in detecting tumor remnants at the time of the initial procedure. We therefore developed the concept of second-look microlaryngoscopies to enable a microscopic and histologic reassessment at the primary tumor site to exclude residual carcinoma. Patients were scheduled for two second-look microlaryngoscopies under general anesthesia at 8-10 weeks and 16-20 weeks after the initial TLS procedure. We analyzed the histopathologic findings of biopsies taken in the second-look microlaryngoscopies and the survival parameters of 181 patients treated with TLS for early laryngeal carcinoma. Carcinoma at the primary site was found in 5.1% of all patients within the first and in 11.5% of all patients within the second second-look microlaryngoscopy, although the preoperative indirect laryngoscopy was inconspicuous in most cases. The survival analysis showed a 5-year and 10-year disease-free survival of 96.3% and 92.7%, respectively. The disease-free survival was significantly decreased when carcinoma was found in the second-look microlaryngoscopy (p=0.004). | 18,839,386 |
Rheological properties of cross-linked hyaluronan-gelatin hydrogels for tissue engineering. | Hydrogels that mimic the natural extracellular matrix (ECM) are used in three-dimensional cell culture, cell therapy, and tissue engineering. A semi-synthetic ECM based on cross-linked hyaluronana offers experimental control of both composition and gel stiffness. The mechanical properties of the ECM in part determine the ultimate cell phenotype. We now describe a rheological study of synthetic ECM hydrogels with storage shear moduli that span three orders of magnitude, from 11 to 3 500 Pa, a range important for engineering of soft tissues. The concentration of the chemically modified HA and the cross-linking density were the main determinants of gel stiffness. Increase in the ratio of thiol-modified gelatin reduced gel stiffness by diluting the effective concentration of the HA component. | 18,839,402 |
Percutaneous ultrasound-guided stenting of the atrial septum in fetal sheep. | Hypoplastic left heart syndrome (HLHS) with a restricitive foramen ovale is associated with high mortality related to fetal left atrial hypertension. Fetal atrial balloon septoplasty has largely failed to achieve adequate decompression due to the small size of the holes produced. We attempted to produce larger atrial communications by stenting the atrial septum in fetal sheep using a minimally invasive technique. We used a percutaneous, ultrasound-guided transpulmonary or transhepatic approach to attempt deployment of coronary stents (2-5 mm in diameter and 13-23 mm in length) in the atrial septum primum of 10 normal fetal sheep. Coronary stents were deployed in eight of the 10 fetal sheep (119-139 days' gestation). The transhepatic route was unsuccessful (n = 2). Transpulmonary implantation was only possible in prone fetuses, so three initially supine fetuses underwent external version. Small coronary stents (2.0-2.5 mm in diameter) were deployed rapidly without complication via an 18G needle (n = 4). Larger coronary stents (5 mm in diameter) were delivered through a 4F sheath, but a right pleural effusion occurred in three of the four cases, related to inferior vena cava injury by the balloon. One stent dislodged from a floppy septum. Another was partially occluded within a week by endocardial cells. Percutaneous ultrasound-guided deployment of coronary stents into the septum primum is feasible without laparotomy or uterine exteriorization in fetal sheep. Partial luminal occlusion by rapid proliferation of endocardial cells is a concern. | 18,839,405 |
Trait anger and anger expression style in children's risky decisions. | In this study, 104 children completed a task, measuring risk decision-making, and the State-Trait Anger Expression Inventory for Children and Adolescents. Subjects were also asked to evaluate the degree of danger, benefit, fun and fear perceived for each risky choice. Analyses indicated that (a) risk decision-making was predicted by both trait anger and outward expression of anger; (b) appraisal of danger fully mediated the relationship between trait anger and risk; (c) perceptions of benefit, scare and fun partially mediated the relationship between trait anger and risk; and (d) appraisal of danger partially mediated the relationship between outward expression of anger and risk decision-making. The results provide evidence for a relationship between dispositional anger and risk decision-making during childhood, suggesting a possible explanation of the mechanisms below. In particular, risk decision-making can be viewed as the output of cognitive and emotive processes, linked to dispositional anger that leads children to be amused, optimistic and fearless in potentially risky situations. These findings substantiate the importance of incorporating cognitive and emotive factors in theories that seek to explain the relationship between personality traits and risk decision-making across a broad age range. | 18,839,406 |
Midgut mitochondrial transhydrogenase in wandering stage larvae of the tobacco hornworm, Manduca sexta. | Midgut mitochondria from fifth larval instar Manduca sexta exhibited a transhydrogenase that catalyzes the following reversible reaction: NADPH + NAD(+) <--> NADP(+) + NADH. The NADPH-forming transhydrogenation occurred as a nonenergy- and energy-linked activity. Energy for the latter was derived from the electron transport-dependent utilization of NADH or succinate, or from Mg++-dependent ATP hydrolysis by ATPase. The NADH-forming and all of the NADPH-forming reactions appeared optimal at pH 7.5, were stable to prolonged dialysis, and displayed thermal lability. N,N'-dicyclohexylcarbodiimide (DCCD) inhibited the NADPH --> NAD(+) and energy-linked NADH --> NADP(+) transhydrogenations, but not the nonenergy-linked NADH --> NADP(+) reaction. Oligomycin only inhibited the ATP-dependent energy-linked activity. The NADH-forming, nonenergy-linked NADPH-forming, and the energy-linked NADPH-forming activities were membrane-associated in M. sexta mitochondria. This is the first demonstration of the reversibility of the M. sexta mitochondrial transhydrogenase and, more importantly, the occurrence of nonenergy-linked and energy-linked NADH --> NADP(+) transhydrogenations. The potential relationship of the transhydrogenase to the mitochondrial, NADPH-utilizing ecdysone-20 monooxygenase of M. sexta is considered. | 18,839,416 |
Co-prescribing azathiopurine or 6-mercaptopurine and 5-aminosalicylate compounds in ulcerative colitis. | A total of 254 senior consultant gastroenterologists with valid e-mail addresses were identified from the membership list of the British Society of Gastroenterology (BSG) 2007. They were sent by e-mail a questionnaire which dealt with aspects of clinical practice and addressed cancer prevention in ulcerative colitis (UC). Replies were received from 97 clinicians (38% response rate). Ninety-one (94%) advised patients with established UC to take 5-aminosalicylate (5-ASA) compounds for life. Seventy-two of the 91 (79%) clinicians co-prescribed 5-ASA compounds with immune modulators for patients with UC. Only 3 clinicians advised patients to take folic acid as a daily supplement. A median of 20% (interquartile range 10%-50%) of their patients with UC were co-prescribed a 5-ASA compound and azathioprine or 6-mercaptopurine. Of these, a median of 3.5% (interquartile 1%-5%) developed neutropenia. Future research needs to be directed at the long-term maintenance treatment and to address questions about which drugs should be used, in what combinations, and with what frequencies. | 18,839,420 |
Gene expression profiles of mucosal fibroblasts from strictured and nonstrictured areas of patients with Crohn's disease. | A frequent complication of Crohn's disease (CD) is the formation of strictures and stenoses. Strictures are characterized by a fibrosis of the bowel wall, induced by abnormal wound healing. Functional changes of colonic lamina propria fibroblasts (CLPF) reflected by increased proliferation and collagen synthesis, increased contractility or reduced migratory potential, indicate a change of the phenotype. We aimed to investigate differences in gene expression profiles between CLPF isolated from normal, inflamed and strictured areas of CD patients. We applied two methods of gene expression analysis, subtractive hybridisation and Affimetrix microarrays to find differences in mRNA expression patterns. Findings were verified by dot blot analysis. Using subtractive screening and dot blot analysis 74 clones could be confirmed to be differentially expressed in CD CLPF from nonstrictured areas compared to control CLPF. Fibronectin (transcript variant 1, NM_002026) could be confirmed as being upregulated in CD with a ratio of 143. Collagen (type I, NM_000089) was upregulated in CD with a ratio of 17.41 clones could be confirmed as differentially expressed in CD CLPF derived from strictures compared to control CLPF. Five clones were identified as chitinase 3-like 1 (cartilage glycoprotein-39) and confirmed with dot blot with a ratio of 2.1.In an independent approach, microarray analysis showed upregulation of chitinase 3-like 1 (signal log ratio 1.9) in CD CLPF from strictures compared to control CLPF thus confirming subtractive hybridization. In the light of the current literature a number of interesting candidates resulted from the multiplicity of identified genes. In regard to the functional changes of CLPF during stenosis and other dysfunctions some proteins might represent a therapeutic target. | 18,839,425 |
Association between plasma thiols and immune activation marker neopterin in stable coronary heart disease. | Studies have associated elevated plasma levels of the thiols homocysteine and cysteine with an increased risk of atherosclerosis. Their relationship with systemic inflammatory parameters and sclerosis scores was investigated in this study. Total homocysteine, total cysteine, neopterin and C-reactive protein (CRP) concentrations were measured in blood samples of 242 patients undergoing elective coronary angiography. A total of 181 patients had coronary artery disease (CAD), as defined by occlusion of > 75% of at least one of the three main coronary arteries, and 61 subjects did not have relevant coronary stenoses. Total cysteine concentrations were higher in patients suffering from coronary artery sclerosis with stepwise increases relative to the extent of coronary artery sclerosis (p < 0.001). In contrast, neither total homocysteine nor the inflammatory markers, CRP and neopterin, differed between patients and controls. However, total homocysteine concentrations correlated with total cysteine (r = 0.468) and neopterin concentrations (r = 0.290), as well as serum creatinine (r = 0.226; all p < 0.001), the latter indicating a dependence of total homocysteine concentrations on kidney function. Total cysteine concentrations were associated with increased neopterin levels (r = 0.231, p < 0.001). Total cysteine concentrations were well suited to estimate the extent of coronary artery sclerosis, while in our study of stable CAD patients total homocysteine was not increased compared to controls. The association between homocysteine, cysteine and parameters of immune activation and inflammation in our study suggests that these markers of CAD may be interdependent. | 18,839,466 |
The effect of the mode of delivery on the maternal-neonatal carnitine blood levels and antioxidant status. | Carnitine blood levels are closely related to beta-oxidation and implicated with strenuous muscle contractions. Normal delivery process is characterized by the participation of the uterus and most skeletal muscles. Women with normal pregnancy (n = 56) were divided into two groups. Group A (n = 26) with normal labor and vaginal delivery and group B (n = 30) with scheduled cesarean section. Blood was obtained from the mothers at the beginning of labor and immediately after delivery (pre- vs. post-delivery), as well as from the cord blood (CB). Total antioxidant status (TAS) was measured with a commercial kit and carnitine was measured in blood spots on Guthrie cards with tandem-mass spectrometry. TAS and carnitine levels were similar in all the groups pre-delivery. In contrast, TAS and carnitine levels were significantly lower in group A than in group B post-delivery. Remarkably lower TAS and carnitine levels were measured in the CB of neonates of group A as compared to the CB of neonates of group B. The lower TAS and carnitine levels measured in group A as compared to group B postdelivery may be due to uterus and skeletal muscle contraction during a normal labor process. Infants born with scheduled cesarean section are benefited with high carnitine levels to face oxidation perinatally. | 18,839,469 |
Time to reconsider the clinical value of immunoglobulin G4 to foods? | The usefulness of serum antibodies to common food antigens (immunoglobulin G4; IgG4) assay in management of patients suffering from food intolerance was assessed. A total of 22 asymptomatic healthy subjects and 68 patients with symptoms referred for suspected food intolerance were studied. Serum IgG4 to 19 common foods was measured by an automated immunoassay. The area under the receiver operating characteristic curve was 0.92 (standard error 0.04) and, at a threshold value of 2.3 U/mL, the IgG4 determination had a sensitivity of 0.81, with a specificity of 0.87. With a pre-test probability of 5% and 20%, the post-test probability of having disease was found to be 24% and 61%, respectively, and 1.1% and 5% if the result was negative. Cohen's K value (0.83) indicated a good agreement between symptoms and IgG4 concentrations. Serum IgG4 assay may play a role in rul-ing out food intolerance, because of its satisfactory negative predictive value (0.99). | 18,839,470 |
Microflora of bile aspirates in patients with acute cholecystitis with or without cholelithiasis: a tropical experience. | The current study determined the spectrum of biliary microflora with special emphasis on enteric fever organisms in patients with acute cholangitis with and without cholelithiasis or other biliary diseases. The patients were divided into three groups: Group A consisted of patients with acute cholecystitis with cholelithiasis; Group B consisted of patients with acute cholecystitis with gastrointestinal ailments requiring biliary drainage and group C consisted of patients with gallbladder carcinoma. Gallbladder, bile and gallstones were subjected to complete microbiological and histopathological examination. Antimicrobial susceptibility of the isolates was performed as per CLSI guidelines. Bacteria were recovered from 17 samples (32%) in Group A, 17 (51.4%) in Group B and 1 (1.6%) in Group C. The most common organisms isolated were Escherichia coli (11, 29.7%), Klebsiella pneumoniae (10, 27%), Citrobacter freundii (3, 8.1%), Salmonella enterica serovar Typhi (3, 8.1%), etc. The majority of Enterobacteriaceae isolates were susceptible to piperacillin-tazobactam and meropenem. As regards Salmonella spp., S. Typhi was isolated from 2 (3.8%) patients in Group A and 1 (16%) in Group C. Antimicrobial susceptibility of potential causative organisms, the severity of the cholecystitis, and the local susceptibility pattern must be taken into consideration when prescribing drugs. A protocol regarding the management of such cases should be formulated based on observations of similar studies. | 18,839,486 |
[Cell cycle alterations of human embryo lung fibroblasts induced by benzo(a)pyrene is positively regulated by cyclin D1 and CDK4]. | To study the effects of benzo(a)pyrene (B(a)P) on the cell cycle distributions and expression of cell cycle regulated protein cyclin D1 and CDK4 in human embryo lung fibroblasts (HELF), and to investigate the relationship between the expression of both cyclin D1 and CDK4 proteins and the cell cycle alterations. Antisense cyclin D1 cDNA and antisense CDK4 cDNA were respectively transfected into HELF cells, and two stable transfectants were established. The protein expression levels of cyclin D1 and CDK4 were detected by western-blotting assay when HELF were treated with B(a)P at the doses of 0.1, 0.5, 2.5 and 12.5 micromol/L B(a)P for 24h. And the flow cytometry assay was used for detecting the cell cycle effects in HELF cells and two stable transfectants. Two cell lines respectively expressed antisense cyclin D1 RNA and antisense CDK4 RNA were successively established in the present study. The protein expressions of cyclin D1 were greatly increased by B(a)P treatment, whereas B(a)P had no significant effects on the protein levels of CDK4. The cell cycle distributions were significantly altered at the level of 2.5 micromol/L B(a)P for 24h treatment. The cell numbers in G1 phase significantly decreased. However, the cell numbers in S phase significantly increased. Cyclin D1 and CDK4 could be active genes and could positively regulate the cell cycle alterations induced by B(a)P. | 18,839,518 |
[CBS gene variations and serum homocysteine level associated with congenital heart defects]. | To study the relationship between two common CBS gene variations, tHcy level and CHDs in a nuclear family-based study. 234 Chinese CHDs patients and their biological parents were recruited as case groups. And another 136 normal individuals and their parents were recruited as controls. The CBS gene 844ins68 and G919A variants were analyzed by PCR and PCR-ARMS methods. The serum fasting total homocysteine (tHcy) level was detected by Fluorescence Polarization Immunoassay. CBS 844ins68 variant was associated with high risk of CHDs, the odds ratios (ORs) between heterozygotes (DI) versus wild homozygotes (DD) were 14.19 (95% CI: 2.21-591.52), 4.37 (95% CI: 1.24-23.47) and 4.77 (95% CI: 1.38-25.37) in mothers, fathers and offspring respectively (P < 0.05). CBS G919A was significantly associated with low risk of CHDs. The ORs of offspring between heterozygotes (GA) and mutant homozygotes (AA) versus wild homozygotes (GG) were 0.45 (95% CI: 0.23-0.87) and 0.34 (95% CI: 0.11-1.01), P < 0.05. And the parents carrying GA and AA genotypes also was lower risk of CHDs. For both of above two variants, the significant relations occurred especially in ventricular septal defect subgroup. Genotype combination analysis showed the more risk alleles (I and G) the family members carried, the higher the offspring risk of CHDs. And the serum fasting tHcy level was not significantly different among various groups and genotypes. CBS gene 844ins68 and G919A variations in nuclear families could be associated with CHDs risk of offspring, but not with serum fasting tHcy level. | 18,839,533 |
[Survey of the dietary status and physical activity level and fitness of college freshmen in Chengdu]. | To study the effect of diet and physical activity on the physical fitness of college students. 1200 freshmen come from different five universities in Chengdu were random recruited chosen (600 males and 600 females). A semi-quantitative food frequency questionnaire and international physical activity questionnaire were used, and meanwhile the fitness test was performed. Micronutrients of iron, zinc, selenium, vitamin E could play important roles in college student fitness. The physical activity level, the time of sitting and the body component could affect college student fitness. Physical activity and diet proved to contribute a lot to the general fitness test system, which is helpful for college students to form healthy habits. | 18,839,540 |
[Effects of simulated wetland water change on the decomposition and nitrogen dynamics of Calamagrostis angustifolia litter]. | From May 2005 to September 2006, the potential effects of wetland water change on the decomposition and nitrogen (N) dynamics of the typical meadow Calamagrostis angustifolia (TMC) and marsh meadow C. angustifolia (MMC) litters were studied by litterbag technique in the typical depressional wetland in the Sanjiang Plain. In this study, the natural water gradient in the depressional wetland was applied to simulate the changes of wetland water conditions, and six decomposition sub-zones were laid in turn in the six communities, Carex pseudocuraica (PF), Carex lasiocarpa (MG), Carex meyeriana (WL), Marsh meadow C. angustifolia (XII), Typical meadow C. angustfolia (XI), and Island forest (DZL), along the water gradient. The results show that water condition has significant effects on the decomposition of litters. If the hydrous environment is formed in C. angustfolia wetland due to the change of precipitation pattern in the future, the litter weightless rates of TMC and MMC will increase 4.33%-16.76% and 24.84%-53.97%, the decomposition rates will increase 10.51%-32.73% and 77.85%-93.92%, and the 95% decomposition time will decrease 0.72-1.85 a and 3.67-4.05 a, respectively. The changes of N contents and N accumulation indices of TMC and MMC litters are relatively consistent, but the change patterns indifferent sub-zones are different. In general, the N in litters in DZL, XI, WL, MG and PF sub-zones show the alternant change characteristics of release and accumulation, but the release process is predominated. In contrast with that, the N in litters in XII sub-zone show release at all times. The C/N ratios have important regulation functions to the changes of N in litters in decomposition process. The estimation results show that the N standing crops of TMC and MMC litters are 12.75 g x m(-2) and 8.29 g x m(-2), and the N annual returning amounts are larger than 1.95 g x (m2 x a)(-1) and 2.25 g x (m2 x a)(-1), respectively. The studies of affecting factors indicate that temperature has promotion effects on the relative decomposition rates of litters, while water condition has restraint effects on them. Further analysis shows that the relative decomposition rates, to some extent, depend on the substrate quality of litters if the nutrient status of decomposition environment does not change greatly. In reverse, if the nutrient status of decomposition environment changes greatly, the relative decomposition rates, to some extent, depend on the supply status of nutrient in decomposition environment. | 18,839,554 |
[Hydro-chemical characteristics in the Danjiangkou Reservoir (water source area of the middle route of the south to north water transfer project), China]. | TDS, pH and major ions in the Danjiangkou Reservoir, the water source area of the Middle Route of the South to North Water Transfer Project of China were monitored during the period of 2004-2006 to systemically analyze hydro-chemical characteristics and water chemistry type. Analysis of variance (ANOVA) and correlation analysis were performed to explore their spatio-temporal pattern. The results show that the water is of low mineralized degree with a total dissolved solid ranging from 149.9-291.2 mg x L(-1), and soft water with a total hardness ranging from 40-50 mg x L(-1) x HCO3- accounts for 77.54%-77.87% of the total major anions with a content of 122.5-170.0 mg x L(-1), while Ca2+ accounts for 70.66%-77.93% of the total major cations with a content of 37.1-43.2 mg x L(-1), and the water is of a HCO3- -Ca type. Major ions show similar spatial variations, decreasing downstream in the Danjiang Reservoir, and reaching the lowest values in the Hanjiang Reservoir. The temporal and seasonal variations of the hydro-chemical characteristics show that the concentrations of major ions in the dry season are larger than those in the wet season. Hydro-chemical characteristics in the reservoir are mainly determined by the rock weatherization, while and anthropogenic activities in the upper-stream and the reservoir region have been influencing the NO3- concentration. Finally, conservation strategies of water resource in the reservoir and its upper stream are discussed. | 18,839,558 |
[Dynamic rule of organic matter removal in vertical-flow constructed wetland]. | Based upon the analysis of the removal rate and form change of the organic pollutants with the different height of the vertical-flow constructed wetland, it comes to the conclusion of the average longitudinal removal rate of variant forms organics and presents the influent concentration and the hydraulic load curve. The results indicated that: Under this experimental condition, the reduction of the organics in the vertical subsurface flow constructed wetland mainly occurred within the 0-10 cm substrate below the pipe distributor. In the meantime, the smaller the hydraulic load of influent, the higher the removal ratio of the organic pollutants in the substrate section. Under the condition that the vertical subsurface flow constructed wetland used the coarse sands as the substrate and kept the influent hydraulic load less than or equal to 0.5 m3/(m2 x d), the effective height of the organics removal was 60 cm. It also showed that the average degradation rate of different kinds of the organic pollutants has a maximum value in the 0-10 cm substrate section below the pipeline. Moreover, the degradation ratio of different kinds of the organics is in significant decreasing tendency with increasing the depth of the longitudinal direction along the pipe. Using sands as the substrate in the vertical subsurface flow constructed wetland, the relationship of the influent concentration and influent hydraulic load can be expressed by formula:(c(in) - c(out)) x q = 1107.02-2.96 c(in) x q. | 18,839,567 |
[Promoting high-temperature hydrolysis under alkaline condition]. | The effect of alkaline thermal hydrolysis method on excess sludge and its characteristic parameters(such as soluble chemical oxygen demand, volatile fatty acids, ammonia-nitrogen, pH value, sludge concentration, etc.) were investigated. The results show that the addition of alkali can reduce the resistance of the sludge cells to high temperature and enhance the release and the hydrolysis of organic materials from the sludge cells with the increase of temperature, pH value and reaction time. The concentration of SCOD reached 17,950 mg/L and SCOD/TCOD was 0.65 on the conditions of pH 13, 170 degrees C and 75 min. The maximal dissolving rate of suspended solids (SS) was 67% and 72% for volatile suspended solids (VSS) at pH 13 with 60 min. The concentration of SCOD after alkaline thermal hydrolysis treatment increased with the increase of sludge concentration, in which the nice linear relation was reached and the correlation coefficient (R2) was above 0.97. The increasing rate of the SCOD was improving with the increase of the pH value and the SCOD of unit sludge reached 672 mg/g at pH 13. The effect of three factors on the SCOD was investigated through orthogonal experiment at the temperature of 170 degrees C, the importance was sludge concentration,pH value and reaction time in turn. | 18,839,582 |
[Content of soil heavy metals and characteristics of environmental quality in tea plantations of Changsha Baili Tea Zone]. | The distributing and changing characteristics and content of soil heavy metals was studied using methods of field survey and sampling, indoor analysis, and pollution index were used to investigate the soil environmental quality in the tea plantations of Changsha Baili Tea Zone. The results showed that the content of soil total Pb, Hg, Cd, Cr, As, Ni basically was in the soil background value, their averages were 42.7, 0.068, 0.074, 92.2, 12.4 and 19.5 mg/kg respectively. The content of heavy metals was lower than the standard of Environmental Qualification of Nuisance Free Tea Producing Area (NY 5020-2001). Simultaneity, soil environmental quality in tea plantations of Baili Tea Zone, it answered for the second grade of State Environmental Quality Standard for Soils (GB 15618-1995), achieved safe class, and the content of soil Hg, Cd, Ni accorded to the first grade of GB 15618-1995, these results showed the Changsha Baili Tea Zone were propitious to develop nuisance free tea production. Besides the single pollution index of Cr was 0.837 and in warning class at the tea plantation of Xiangfeng, the others were all less than 0.7, and in the safe class. The integrated index of 6 tea bases was all less than 0.7, in the safe class, the soil environmental quality was cleanness on the whole at Changsha Baili Tea Zone, and the soils were suitable for non-polluted agricultural production. | 18,839,593 |
[Assessment of health risk for mined soils based on critical thresholds for lead, zinc, cadmium and copper]. | Contents of heavy metals (Pb, Zn, Cd, Cu) in soils in terms of point, line and area around a lead/zinc mine in Dongguan town, Zhejiang, China, were investigated to evaluate environmental quality based on index and health risk assessment model for safety of soils-human. The order for average contents of Pb, Zn, Cd, Cu in terms of point, line and area were Pb >> Zn >> Cu >> Cd. The contents of Pb, Zn, Cd, Cu in terms of point and line were much higher than that in terms of area, especially Pb and Zn contents. The distribution of soil heavy metals was asymmetric. The calculated critical threshold in soil for adult was higher than that for children. The average order of individual risk index for children and adult health was Pb >> Cd > Cu > Zn. Children were more easily affected by soil heavy metals, for that hazard indexes for children were 3 times of adult health. The environmental quality of Dongguan town was mainly safe correspondingly. The heavy metal environmental quality in terms of point and line near a lead/zinc mine had higher hazard risk and might bring potential hazard to local residents. | 18,839,594 |
[Effect of Cd on remediation of DDT contaminated soil using different laccase forms]. | This study investigated the effect of Cd on remediation of DDT contaminated soil using free laccase and immobilized reversed micelles laccase. The results show: degradation rates of ingredients of DDT and total DDT reduced with increasing of Cd concentration, the higher percentage of components in total DDT, the greater impact of Cd on them. Degradation rates of different components were p, p'-DDT > p, p'-DDD > o,p'-DDT > p, p'-DDE. When Cd concentration was 0, 0.5, 1 and 2 mg x kg(-1), the responding degradation rates of DDTs were measured at 50.68%, 32.50%, 14.92% and 13.40%, respectively. Compared with free laccase, degradation rate of total DDT by immobilized reversed micelles laccase nearly increased by 20% in soil without Cd and 30% in soil with 0.5 mg x kg(-1) Cd, implying that immobilized reversed micelles laccase is more effective for DDT degradation than free laccase. | 18,839,595 |
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